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To describe and explain sex differences in antihypertensive drug use.From 1987 to 1995, two cross-sectional population-based surveys of cardiovascular disease risk factors in The Netherlands were carried out among 56 026 men and women aged 20–59 years. Polytomous logistic regression modelling was used to adjust for potential confounders of the association between sex and use of different antihypertensive drugs.The response rate was 40% for men and 46% for women. Of these respondents, 40% (1041) of the hypertensive men and 59% (1403) of the hypertensive women were being treated pharmacologically; 57% (595) of the treated men and 54% (760) of the treated women were on monotherapy for hypertension with a diuretic (men 14.8%, women 37.2%), a β-blocker (men 59.0%, women 45.3%), a calcium antagonist (men 8.6%, women 5.0%) or an angiotensin converting enzyme inhibitor (men 17.7%, women 12.5%). Among those on monotherapy for hypertension, women were less likely than men to be using a β-blocker [prevalence odds ratio (POR), female/male = 0.34; 95% confidence interval (CI) 0.24–0.47], a calcium antagonist (POR = 0.27, 95% CI 0.15–0.48) or an angiotensin converting enzyme inhibitor (POR = 0.34, 95% CI 0.22–0.52) than a diuretic. These sex differences persisted after adjustment for all factors that could have influenced the choice of these antihypertensive drugs (indications and contra-indications for the four antihypertensive drug classes). The sex differences in antihypertensive drug use were smaller among hypertensives with a history of cardiovascular disease (adjusted PORs, female/male, for β-blockers, calcium antagonists and ACE inhibitors, respectively, compared to diuretics were 0.80 with 95% CI 0.20–3.24, 0.40 with 95% CI 0.10–0.48 and 0.64 with 95% CI 0.12–3.39) than among those without such a history.The different patterns of antihypertensive drug use among hypertensive men and women seem irrational, and cannot be explained by factors known to influence antihypertensive drug choice. Among hypertensives with a history of cardiovascular disease, the sex differences were smaller than among those without such a history. Further research is required to explain the sex differences in the choice of antihypertensive drug by prescribers, and to investigate the consequences of these differences for long-term patient outcomes.