Aims: A recent meta-analysis of clinical trials has demonstrated a small excess of cancers in persons that had been allocated to angiotensin-receptor blockers (ARBs). We undertook this observational study to look at dose-response and dose-duration effects and look for specificity with respect to outcome. Use of angiotensin converting enzyme inhibitors (ACEIs) was included in the main analysis since ACEIs share pharmacological properties with ARBs. Methods: We identified 149,417 incident cancer cases in Denmark during the period 2000-2005. Four controls, matched by age and gender, were selected for each case by a risk-set sampling. Data on medication was retrieved from the Danish National Prescription Registry. We defined long-term exposure as at least 1000 defined daily doses redeemed within the past five years. Confounders were controlled by conditional logistic regression. Results: The odds ratio (OR) associating long-term drug use with incident cancer was 1.12 (95% CI: 1.06-1.18), 1.17 (95% CI: 1.14-1.20), 1.23 (95% CI: 1.20-1.26), 1.18 (95% CI: 1.14-1.22), 1.25 (95% CI: 1.22-1.28), 1.37 (95% CI: 1.21-1.54), 1.29 (95% CI: 1.22-1.37) for ARB, ACEI, calcium channel blockers, beta blockers, thiazide diuretics and alfa blockers. No consistent dose-duration or dose-response association could be demonstrated for ARB or ACEI. Conclusion: The indication or possibly threshold for prescribing antihypertensives appears to be related to a small increase in cancer risk. The ARB-cancer association is probably too weak to be addressed in observational studies, given their limitations. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.