BackgroundHypertension Canada 2017 guidelines favoured the use of thiazide (TZ)-like diuretics, such as CLTD (chlorthalidone) and indapamide (IND) over hydrochlorothiazide (HCTZ). Health Canada warned in 2019 that HCTZ may be associated with increased risk of skin cancer. Our study looked at the changes in TZ prescriptions from 2015 to 2021 in Ontario, Canada. MethodsA retrospective cohort study was conducted of adults with hypertension, using electronic medical record data from the University of Toronto Practice-Based Research Network database covering mostly the Greater Toronto area. Outcomes included the proportion of patients who received a prescription of HCTZ, CLTD, or IND each month. Interrupted time-series analysis was used to evaluate the change in outcomes after publication of the 2017 guidelines and 2019 safety warning. Prescription trends were stratified by prescribing physicians’ sex and year of medical school graduation. ResultsA total of 100,428 patients with hypertension were included in the cohort, with 31,700 patients who received at least one TZ prescription from 343 family physicians. We found a declining trend in HCTZ prescriptions over time, accompanied by an increase in IND and CLTD prescriptions, with statistically significant but transient changes in prescription rates after publication of the 2017 guidelines and the 2019 safety warning for all 3 medications. Female physician and early-career physician prescription rates changed faster than that of their counterparts immediately after the Health Canada safety warning was issued. ConclusionsTZ diuretic prescription patterns have changed in recent years, but Hypertension Canada’s 2017 guidelines and the 2019 Health Canada safety warning did not have a sustained significant impact on the change in prescription rates of HCTZ, IND, and CLTD.