The objective was to assess persistence with antihypertensive therapy (AHT) and discontinuation patterns in patients newly dispensed different antihypertensive drug classes in a natural Canadian population-based setting. Hypertensive patients initiating AHT monotherapy were included in this 3-year retrospective cohort study (N=21 326) using the Saskatchewan health-care databases. Persistence was defined as consistently refilling a new prescription for AHT within 90 days of a previous dispensing. New courses of AHT were also documented in nonpersistent patients. Kaplan-Meier and Cox regression analyses were used to compare persistence and new courses of therapy across initial drugs. Compared to the newer angiotensin II antagonists (AIIAs), the likelihood of discontinuing therapy over the 39-month study period was significantly higher for angiotensin-converting enzymes inhibitors (HR=1.29; 95% CI=1.16-1.43), calcium channel blockers (HR=1.42; 95% CI=1.27-1.60), beta blockers (HR=1.62; 95% CI=1.45-1.80) and diuretics (HR=1.92; 95% CI=1.73-2.14). In the year following treatment discontinuation, between 54 and 75% of patients initiated a second course of treatment. Patients initiated on an AIIA had a significantly higher likelihood of starting a new course of therapy after a first treatment discontinuation, compared to all other agents. In conclusion, hypertensive patients initiated on an AIIA not only had greater persistence to AHT but were also more likely to initiate a new course of AHT after discontinuation than those initiating treatment with other agents. Further studies are required that relate intermittent treatment behaviours to health outcomes and costs in hypertension.