Although several studies suggest that the prognosis of hypertensive dialysis patients can be improved by using antihypertensive drug therapy, it is unknown whether the prescription of a particular class or combination of antihypertensive drugs is beneficial during hemodialysis. Methods: We performed a propensity score matching study to compare the effectiveness of various classes of antihypertensive drugs on cardiovascular (CV) mortality in 2518 incident hemodialysis patients in Spain. The patients had initially received antihypertensive therapy with a renin-angiotensin system (RAS) blocker (728 patients), a ß-blocker (679 patients), antihypertensive drugs other than a RAS blocker or a ß-blocker (787 patients), or the combination of a ß-blocker and a RAS inhibitor (324 patients). These patients were followed for a maximum of 5 years (median: 2.21 yr; range: 1.04–3.34 yr). Results: After adjustment for baseline CV risk covariates, no significant differences were observed in the risk of CV mortality between patients taking a RAS blocker and patients treated with ß-blocker–based antihypertensive therapy. The combination of a RAS blocker with a ß-blocker was associated with better CV survival than either agent alone (RAS blocker: hazard ratio [HR]: 1.68; 95% confidence interval [CI] 1.05–2.69; ß-blocker: HR: 1.59; 95% CI: 1.01–2.50; antihypertensive medication other than a RAS blocker or ß-blocker: HR: 1.67; 95% CI: 1.08–2.58). Discussion: Our data suggested that the combination of a RAS blocker and a ß-blocker could improve survival in hemodialysis patients. Further prospective randomized controlled trials are necessary to confirm the beneficial effects of this combination of antihypertensive drugs in patients undergoing hemodialysis.