Background: Treatment decisions in clinical cardiology are directed by results from randomized clinical trials (RCTs). We studied the appropriateness of the use and interpretation of subgroup analysis in current therapeutic cardiovascular RCTs. Methods: We reviewed main reports of phase 3 cardiovascular RCTs with at least 100 patients, published in 2002 and 2004, and from major journals (Circulation, J Am Coll Cardiol, Am Heart J, Am J Cardiol, N Engl J Med, Lancet, JAMA, BMJ, Ann Intern Med). Information on subgroups included prespecification, number, interaction test use, significant subgroups found, and emphasis on findings. We examined appropriateness of reporting and differences according to sample size, overall trial result, and CONSORT adoption. Results: We selected 63 RCTs, with a median of 496 (range 100-15 245) patients. Thirty-nine RCTs were reported with subgroup analyses and 26 with >5 subgroups. No trial was specifically powered to detect subgroup effects, and only 14 RCTs were reported with fully prespecified subgroups. Only 11 RCTs were reported with interaction tests. Furthermore, 21 RCTs were reported with claims of significant subgroups and 15 with equal or more emphasis to subgroups than to the overall results. Subgroup analyses in large RCTs (>500 patients) were reported more often than in small ones (24/30 vs 15/33, P = .005). No differences were found according to overall result (positive/negative) or CONSORT adoption. Conclusions: Subgroup analyses in recent cardiovascular RCTs were reported with several shortcomings, including a lack of prespecification and testing of a large number of subgroups without the use of the statistically appropriate test for interaction. Reporting of subgroup analysis needs to be substantially improved because emphasis on these secondary results may mislead treatment decisions.