Studies have reported conflicting results on the association between the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and cancer development. We compared the incidence of cancer between patients using RAAS inhibitors and other antihypertensive drugs. This retrospective observational cohort study used data from seven hospitals in Korea that were converted for use in the Observational Medical Outcomes Partnership Common Data Model. A total of 166,071 patients on antihypertensive therapy across the databases of the seven hospitals were divided into two groups according to the use of RAAS inhibitors. The primary outcome was the occurrence of cancer. A total of 166,071 patients across the databases of the seven hospitals was included in the final analysis; 26,650 (16%) were in the RAAS inhibitors group and 139,421 (84%) in the other antihypertensive drugs group. The meta-analysis of the whole cohort showed a lower incidence of cancer occurrence in the RAAS inhibitor group (9.90 vs. 13.28 per 1000 person years; HR, 0.81; 95% confidence interval [CI], 0.75-0.88). After propensity-score matching, the RAAS inhibitor group consistently showed a lower incidence of cancer (9.90 vs. 13.28 per 1000 person years; HR, 0.86; 95% CI, 0.81-0.91). The patients using RAAS inhibitors showed a lower incidence of cancer compared with those using other antihypertensive drugs. These findings support the association between the use of RAAS inhibitors and cancer occurrence.