We conducted a systematic review of randomized, controlled, monotherapy trials since 1990 of oral antihypertensive agents in patients with essential hypertension. Our objective was to quantify the frequency of discontinuation of antihypertensive agents due to adverse events from a meta-analysis of the studies. A total of 190 studies met inclusion criteria. The highest frequency of discontinuations due to adverse events (DAEs) occurred with calcium channel blockers (6.7%) and alpha-adrenergic blockers (6.0%); the lowest with diuretics and angiotensin receptor blockers (each 3.1%). Only in calcium channel blocker studies was the frequency of DAEs greater in treated patients than in patients receiving placebo, but the difference was not significant. This systematic review suggests that the frequency of DAEs in monotherapy antihypertensive trials varies across drug classes and should be considered when choosing drugs for patients with essential hypertension.