Purpose: To compare low-dose thiazides to β -blockers, angiotensin converting enzyme (ACE) inhibitors, calcium antagonists and a-blockers for simplicity, tolerability, efficacy, safety and cost-effectiveness as first-line treatment for hypertension. Method: Review of short-term comparative studies, and the outcome of long-term trials with vascular complications of hypertension as endpoints. Simplicity: Among the advantages of thiazides are a flat dose-reponse; no dose titration; effectiveness when used once a day; no first-dose hypotension; and few contra-indications. Tolerability: Thiazides are the best tolerated agents in patients over the age of 60 years and in younger women. They sometimes cause gout and impotence in younger men, in whom p-blockers are equally acceptable first-line therapy. Efficacy: Thiazide-based regimens have consistently reduced vascular complications of hypertension, the real measure of efficacy. There is little evidence that regimens based on other drugs are effective in this sense. Safety: Concerns that thiazide-induced biochemical changes cause coronary events are baseless. An overview of outcome trials shows that thiazide-based treatment reduces coronary events significantly, and the reduction is not significantly different from that predicted by epidemiological data. Thiazide-based therapy has also reduced coronary events significantly and substantially in elderly patients with isolated systolic hypertension. Cost-effectiveness: Low-dose thiazide treatment needs minimal monitoring, and has proved most cost-effective in formal analyses. Conclusion: Low-dose thiazide treatment is a clear first-line choice for patients aged over 60 years and younger women, except those with diabetes or gout. In younger men there is little to choose between thiazides and β-blockers. © Current Science Ltd.