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Objective To describe patterns of persistence and related primary care costs associated with first antihypertensive treatment. Design and setting Retrospective cohort study during 2000–2001, using information from 320 Italian general practitioners. Participants We studied 13 303 patients with newly diagnosed hypertension, who received a first single antihypertensive prescription within 3 months after diagnosis. Main outcome measures Persistence with first-line single treatment, categorized as follows: continuers: patients continuing the first-line medication for at least 1 year; combiners: patients receiving an additional antihypertensive drug and continuing the initial medication; switchers: patients changing from the first-line to another class of antihypertensive drug and discontinuing the initial treatment; discontinuers: patients stopping the first-line treatment without having another prescription until the end of the follow-up. Primary care costs were expressed as the cost of hypertension management per person-year of follow-up. Results In the study cohort, 19.8% were continuers, 22.1% were combiners, 15.4% were switchers, and 42.6% were discontinuers. Continuation was greatest with angiotensin II type 1 receptor blocking agents (25.2%), calcium channel blockers (23.9%) and angiotensin-converting enzyme inhibitors (23.3%). Severe hypertension [hazards ratio 1.30; 95% confidence interval (CI) 1.18 to 1.43] and severe health status (hazards ratio 1.22; 95% CI 1.15 to 1.30) increased the risk of discontinuation. The likelihood of needing an additional antihypertensive drug was associated with mildto- severe baseline blood pressure, diabetes (hazards ratio 1.20; 95% CI 1.06 to 1.36), and familial history of cardiovascular disease (hazards ratio 1.24; 95% CI 1.10 to 1.39). Discontinuers accounted for 22.4% of the total primary care cost. Initial treatment with angiotensin II type 1 receptor blocking agents and b-blockers resulted in incremental primary care costs of s145.2 and s144.2, respectively, compared with diuretics. Combiners and switchers increased the primary care cost by s140.1 and s11.7, compared with continuers. Conclusion Persistence with first-line single antihypertensive drugs is extremely low during the first year of treatment. Potential cost saving should be possible by reducing the high frequency of discontinuation. Diuretics represent the least expensive therapeutic option, although further investigations in the long-term are needed to analyse the effects of persistence on therapeutic effectiveness and related costs. J Hypertens 23:2093–2100