When subgroup analyses are not correctly analyzed and reported, incorrect conclusions may be drawn, and inappropriate treatments provided. Despite the increased recognition of the importance of subgroup analysis, little information exists regarding the prevalence, appropriateness, and study characteristics that influence subgroup analysis. The objective of this study is to determine (1) if the use of subgroup analyses and multivariable risk indices has increased, (2) whether statistical methodology has improved over time, and (3) which study characteristics predict subgroup analysis.We randomly selected randomized controlled trials (RCTs) from five high-impact general medical journals during three time periods. Data from these articles were abstracted in duplicate using standard forms and a standard protocol. Subgroup analysis was defined as reporting any subgroup effect. Appropriate methods for subgroup analysis included a formal test for heterogeneity or interaction across treatment-by-covariate groups. We used logistic regression to determine the variables significantly associated with any subgroup analysis or, among RCTs reporting subgroup analyses, using appropriate methodology.The final sample of 416 articles reported 437 RCTs, of which 270 (62 %) reported subgroup analysis. Among these, 185 (69 %) used appropriate methods to conduct such analyses. Subgroup analysis was reported in 62, 55, and 67 % of the articles from 2007, 2010, and 2013, respectively. The percentage using appropriate methods decreased over the three time points from 77 % in 2007 to 63 % in 2013 (p < 0.05). Significant predictors of reporting subgroup analysis included industry funding (OR 1.94 (95 % CI 1.17, 3.21)), sample size (OR 1.98 per quintile (1.64, 2.40), and a significant primary outcome (OR 0.55 (0.33, 0.92)). The use of appropriate methods to conduct subgroup analysis decreased by year (OR 0.88 (0.76, 1.00)) and was less common with industry funding (OR 0.35 (0.18, 0.70)). Only 33 (18 %) of the RCTs examined subgroup effects using a multivariable risk index.While we found no significant increase in the reporting of subgroup analysis over time, our results show a significant decrease in the reporting of subgroup analyses using appropriate methods during recent years. Industry-sponsored trials may more commonly report subgroup analyses, but without utilizing appropriate methods. Suboptimal reporting of subgroup effects may impact optimal physician-patient decision-making.