A modest (41%) reduction in abdominal aortic aneurysm (AAA) growth rate is likely to delay AAA-related events (surgery or rupture) by 5 years, making the notion of AAA medical treatment very appealing. Randomized controlled trials of commonly used existing medications are expensive and ethically questionable. This study reviewed the independent associations of commonly used medications and AAA growth during a 25-year period of AAA surveillance. The study included all patients monitored through an AAA screening and surveillance program. Records of AAA size, risk factors, outcomes, death, and medications were entered into a continually updated database. AAA growth rates were calculated using a flexible hierarchical model. A multivariate model was used to test for associations independent of confounders. The study comprised 1269 patients (94.1% men) who had a mean age of 67 years. The median starting diameter was 35 mm, the end diameter was 44 mm, and follow-up was 3.4 years. Drugs used in the treatment of diabetes were associated with a 56% reduction in AAA growth rate (P = .01) independent of confounding factors, including other therapeutic agents (P = .003). Angiotensin-receptor blockers and potassium-sparing diuretics were also associated with slower AAA growth rates, although these effects were not independent of all confounders. Diabetes or its medications, or both, have a negative effect on AAA growth. Because of polypharmacy, demonstrating the independent effects of individual drugs affecting the renin-angiotensin system was not possible. In light of this analysis, however, strong associations between angiotensin-receptor blockers and aldosterone-receptor blockers and slowed AAA progression are credible.