The purpose of this study was to examine the existing research on single-set vs. multiple-set resistance training programs. Using the meta-analytic approach, we included studies that met the following criteria in our analysis: (a) at least 6 subjects per group; (b) subject groups consisting of single-set vs. multiple-set resistance training programs; (c) pretest and posttest strength measures; (d) training programs of 6 weeks or more; (e) apparently "healthy" individuals free from orthopedic limitations; and (f) published studies in English-language journals only. Sixteen studies generated 103 effect sizes (ESs) based on a total of 621 subjects, ranging in age from 15-71 years. Across all designs, intervention strategies, and categories, the pretest to posttest ES in muscular strength was (chi = 1.4 +/- 1.4; 95% confidence interval, 0.41-3.8; p < 0.001). The results of 2 x 2 analysis of variance revealed simple main effects for age, training status (trained vs. untrained), and research design (p < 0.001). No significant main effects were found for sex, program duration, and set end point. Significant interactions were found for training status and program duration (6-16 weeks vs. 17-40 weeks) and number of sets performed (single vs. multiple). The data indicated that trained individuals performing multiple sets generated significantly greater increases in strength (p < 0.001). For programs with an extended duration, multiple sets were superior to single sets (p < 0.05). This quantitative review indicates that single-set programs for an initial short training period in untrained individuals result in similar strength gains as multiple-set programs. However, as progression occurs and higher gains are desired, multiple-set programs are more effective.