Although RCTs are considered the gold standard for the evaluation of the intended effects of medicines, they are less appropriate for determining unintended or unexpected beneficial or adverse effects for several reasons. Data from RCTs of varenicline typically have less than a year of follow-up, with relatively low power to detect effects on clinically-relevant outcomes, and are not informative about the longer-term consequences of varenicline treatment. Furthermore, these RCTs usually exclude smokers with chronic respiratory or heart disease and psychiatric illnesses, so their findings may not be generalisable to all patients. Observational studies using large primary care databases of electronic health records may be used to address these unanswered questions, as the investigators propose to do here.