In October 2013, Mathieson was appointed vice chancellor of the University of Hong Kong, replacing Lap-Chee Tsui.
His appointment was controversial as some staff felt that Mathieson lacked management experience and familiarity with Chinese society.
Leong Che-hung, who headed the committee that appointed Mathieson noted that he had experience running a faculty at the University of Bristol, while Mathieson himself suggested his unfamiliarity with China gave the opportunity for a fresh start.

His tenure at HKU was described to be full of "tension and clashes between the university’s governing body and students".
Five months into his vice-chancellorship, a students-led class boycott, protesting against Beijing authorities' decision of Hong Kong's suffrage, evolved into a 79-day occupy protest.
During the crisis, he stated that independence was not a realistic political option for Hong Kong, but defended the rights of students to protest in favour of Hong Kong's democratic values.

In 2015, Mathieson was elected as an honorary fellow of Hughes Hall, University of Cambridge.
That year, a University of Hong Kong panel led by Mathieson selected Johannes Chan as pro-vice-chancellor, however the appointment was blocked by the university's governing council.
Chan is pro-democracy, supports human rights, and had supported the student occupy protest in 2014, and was unpopular with the government.
The episode was viewed as an incident in which the university's academic freedom was under threat, and Mathieson's authority suffered as a result; in a staff survey, 78% of people did not feel Mathieson had “effectively protected academic freedom”.
Addressing the results of the survey, Mathieson acknowledged the unpopularity of some of his actions and questioned the survey's methodology.

On 2 February 2017, 2 years before the original expiry of his contract, Mathieson resigned from the post of HKU.
Mathieson claimed that he was squeezed out of the position by HKU's Chairman of the Governing Council, Arthur Li.
The Chairman of the Staff Association, William Cheung, stated "you may now appreciate why we thank you [University of Edinburgh] so many times for taking Professor Mathieson on board" after claims that Mathieson failed to uphold academic freedom, discouraged debate on campus, and did not understand the needs of students emerged from a staff survey.
Addressing the results of the survey, Mathieson described the survey as flawed in its methodology.

Contrary to the views above, many in Hong Kong felt that he showed leadership and steered a very diplomatic course between the Hong Kong government, China, students, the university and the citizenry at a complex and difficult time in Hong Kong's history, when the 2014 student 'umbrella movement' emerged and brought the city centre to a standstill.
His over-riding care and concern was for the safety of his students at a time when the movement became violent.
He recognised independence was not a realistic political option for Hong Kong, but defended the rights of students to protest in favour of Hong Kong’s democratic values.
In October 2013, Mathieson was appointed vice chancellor of the University of Hong Kong, replacing Lap-Chee Tsui. His appointment was controversial as some staff felt that Mathieson lacked management experience and familiarity with Chinese society. Leong Che-hung, who headed the committee that appointed Mathieson noted that he had experience running a faculty at the University of Bristol, while Mathieson himself suggested his unfamiliarity with China gave the opportunity for a fresh start.
His tenure at HKU was described to be full of "tension and clashes between the university’s governing body and students". Five months into his vice-chancellorship, a students-led class boycott, protesting against Beijing authorities' decision of Hong Kong's suffrage, evolved into a 79-day occupy protest. During the crisis, he stated that independence was not a realistic political option for Hong Kong, but defended the rights of students to protest in favour of Hong Kong's democratic values.
In 2015, Mathieson was elected as an honorary fellow of Hughes Hall, University of Cambridge. That year, a University of Hong Kong panel led by Mathieson selected Johannes Chan as pro-vice-chancellor, however the appointment was blocked by the university's governing council. Chan is pro-democracy, supports human rights, and had supported the student occupy protest in 2014, and was unpopular with the government. The episode was viewed as an incident in which the university's academic freedom was under threat, and Mathieson's authority suffered as a result; in a staff survey, 78% of people did not feel Mathieson had “effectively protected academic freedom”. Addressing the results of the survey, Mathieson acknowledged the unpopularity of some of his actions and questioned the survey's methodology.
On 2 February 2017, 2 years before the original expiry of his contract, Mathieson resigned from the post of HKU. Mathieson claimed that he was squeezed out of the position by HKU's Chairman of the Governing Council, Arthur Li. The Chairman of the Staff Association, William Cheung, stated "you may now appreciate why we thank you [University of Edinburgh] so many times for taking Professor Mathieson on board" after claims that Mathieson failed to uphold academic freedom, discouraged debate on campus, and did not understand the needs of students emerged from a staff survey. Addressing the results of the survey, Mathieson described the survey as flawed in its methodology.
Contrary to the views above, many in Hong Kong felt that he showed leadership and steered a very diplomatic course between the Hong Kong government, China, students, the university and the citizenry at a complex and difficult time in Hong Kong's history, when the 2014 student 'umbrella movement' emerged and brought the city centre to a standstill. His over-riding care and concern was for the safety of his students at a time when the movement became violent. He recognised independence was not a realistic political option for Hong Kong, but defended the rights of students to protest in favour of Hong Kong’s democratic values.
Peter Mathieson (nephrologist)