Wheeler's nomination to become head of the EPA was confirmed by the Senate in a 52–47 vote in February 2019, in a largely party-line vote.

In 2019, Wheeler argued in favor of a proposed EPA rule that would prohibit the EPA from using studies that do not make raw data publicly available, a rule first proposed under Wheeler's predecessor, Scott Pruitt.
Wheeler framed the proposal as a "transparency" rule; scientists opposed the rule, stating that it would seriously limit the research available to the EPA, because studies do not tend to make personal and confidential information available.
The proposal could prevent EPA from using many important studies underpinning various regulations, including regulations on air pollution.
The proposed rule was denounced by 69 scientific and medical groups (including the American Lung Association, American Medical Association, and American Psychological Association) and the editors of five leading scientific journals (Nature, Cell, PLOS One, and Proceedings of the National Academy of Sciences).
A bipartisan group of former EPA administrators, testifying before the House Energy Subcommittee on Oversight, also criticized proposals to restrict the use of science in EPA decision making.
The EPA's Science Advisory Board also pushed back against the proposal.

In arguing in favor of the proposed rule, Wheeler called on the EPA to use the kind of double-blind studies the FDA uses.
This assertion was criticized by the Union of Concerned Scientists, which described Wheeler's comment as "breath-takingly ignorant" because double-blind studies (study designs in which "both researchers and study subjects don't know which subjects are given the placebo versus the treatment") are possible in drug trials but are infeasible in most of the kind of research the EPA does, i.e. measuring environmental impact.

In March 2020, during the COVID-19 pandemic in the United States, the EPA declared that for an indefinite amount of time, it would generally not fine companies for violating environment regulations for "routine compliance monitoring [of pollution], integrity testing, sampling, laboratory analysis, training, and reporting or certification obligations", if the EPA agreed that the COVID-19 pandemic caused the violation.
Wheeler said that the EPA "recognizes challenges resulting from efforts to protect workers and the public from Covid-19 may directly impact the ability of regulated facilities to meet all federal regulatory requirements."

In April 2020, the EPA declined to raise environmental standards for fine soot pollution (PM 2.5), during a mandated review.
A draft scientific assessment by the EPA had estimated that the current standards (12 micrograms per cubic meter) were "associated with 45,000 deaths" per year, but if the standards were raised (9 micrograms per cubic meter), then 12,150 lives would be saved.
Companies from many industries, producing fossil fuels, automobiles and chemicals, requested that the Trump administration ignore these findings and avoid raising standards.
After the publication of that report, numerous industries, including oil and coal companies, automakers and chemical manufacturers, urged the Trump administration to disregard the findings and not tighten the rule.
The draft of the new rule stated Wheeler placed "little weight on quantitative estimates" of deaths caused by fine soot pollution, reported the New York Times.

Also in April 2020, the EPA weakened mercury regulation in the United States by drastically curtailing the health benefits considered in calculations for making future regulations.
Wheeler declared that this was a "honest accounting method", while the Trump administration took the stance that mercury cleanup was not "appropriate and necessary".
Wheeler's nomination to become head of the EPA was confirmed by the Senate in a 52–47 vote in February 2019, in a largely party-line vote.
In 2019, Wheeler argued in favor of a proposed EPA rule that would prohibit the EPA from using studies that do not make raw data publicly available, a rule first proposed under Wheeler's predecessor, Scott Pruitt. Wheeler framed the proposal as a "transparency" rule; scientists opposed the rule, stating that it would seriously limit the research available to the EPA, because studies do not tend to make personal and confidential information available. The proposal could prevent EPA from using many important studies underpinning various regulations, including regulations on air pollution. The proposed rule was denounced by 69 scientific and medical groups (including the American Lung Association, American Medical Association, and American Psychological Association) and the editors of five leading scientific journals (Nature, Cell, PLOS One, and Proceedings of the National Academy of Sciences). A bipartisan group of former EPA administrators, testifying before the House Energy Subcommittee on Oversight, also criticized proposals to restrict the use of science in EPA decision making. The EPA's Science Advisory Board also pushed back against the proposal.
In arguing in favor of the proposed rule, Wheeler called on the EPA to use the kind of double-blind studies the FDA uses. This assertion was criticized by the Union of Concerned Scientists, which described Wheeler's comment as "breath-takingly ignorant" because double-blind studies (study designs in which "both researchers and study subjects don't know which subjects are given the placebo versus the treatment") are possible in drug trials but are infeasible in most of the kind of research the EPA does, i.e. measuring environmental impact.
In March 2020, during the COVID-19 pandemic in the United States, the EPA declared that for an indefinite amount of time, it would generally not fine companies for violating environment regulations for "routine compliance monitoring [of pollution], integrity testing, sampling, laboratory analysis, training, and reporting or certification obligations", if the EPA agreed that the COVID-19 pandemic caused the violation. Wheeler said that the EPA "recognizes challenges resulting from efforts to protect workers and the public from Covid-19 may directly impact the ability of regulated facilities to meet all federal regulatory requirements."
In April 2020, the EPA declined to raise environmental standards for fine soot pollution (PM 2.5), during a mandated review. A draft scientific assessment by the EPA had estimated that the current standards (12 micrograms per cubic meter) were "associated with 45,000 deaths" per year, but if the standards were raised (9 micrograms per cubic meter), then 12,150 lives would be saved. Companies from many industries, producing fossil fuels, automobiles and chemicals, requested that the Trump administration ignore these findings and avoid raising standards. After the publication of that report, numerous industries, including oil and coal companies, automakers and chemical manufacturers, urged the Trump administration to disregard the findings and not tighten the rule. The draft of the new rule stated Wheeler placed "little weight on quantitative estimates" of deaths caused by fine soot pollution, reported the New York Times.
Also in April 2020, the EPA weakened mercury regulation in the United States by drastically curtailing the health benefits considered in calculations for making future regulations. Wheeler declared that this was a "honest accounting method", while the Trump administration took the stance that mercury cleanup was not "appropriate and necessary".
Andrew R. Wheeler