BACKGROUND The prevalence of diabetes mellitus (DM) has increased exponentially in recent years, with 100 million people expected to develop diabetes in the coming 15 years. The impact of medical therapy on the incidence of new onset DM is not clear. We performed a systematic review and meta-analysis to study the impact of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the incidence of new onset DM. METHODS MEDLINE, EMBASE, BIOSIS, Cochrane databases from inception until February 2009 for randomized controlled trials (RCT) that reported new incident DM with ACEI or ARB therapy. A total of 18 RCT are included in this meta-analysis. A random-effect model was used and between-studies heterogeneity was estimated with I(2). RESULTS There were 50,451 patients randomized to ACEI or ARB and 50,397 patients randomized to other therapies. ACEI/ARB use was associated with a decrease in new onset DM (RR 0.78, 95% CI 0.70-0.88, p = 0.003 for ACEI and RR 0.8, 95% CI 0.75-0.86, p < 0.0001 for ARB). Treating 100 patients with ACEI or 50 patients with ARB prevents one case of new onset DM. CONCLUSIONS The cumulative evidence suggests that the use of ACEI/ARB prevents diabetes mellitus. This finding may be of special clinical benefit in patients with hypertension and prediabetes or metabolic syndrome.