This study reports the results of a meta-analysis of the available literature on the effectiveness of various forms of innovative small-group learning methods on student achievement in undergraduate college health science classrooms. The results of the analysis revealed that most of the primary studies supported the effectiveness of the small-group learning methods in improving students' academic achievement with an overall weighted average effect-size of 0.59 in standard deviation units favoring small-group learning methods. The subgroup analysis showed that the various forms of innovative and reform-based small-group learning interventions appeared to be significantly more effective for students in higher levels of college classes (sophomore, junior, and senior levels), students in other countries (non-U.S.) worldwide, students in groups of four or less, and students who choose their own group. The random-effects meta-regression results revealed that the effect sizes were influenced significantly by the instructional duration of the primary studies. This means that studies with longer hours of instruction yielded higher effect sizes and on average every 1 h increase in instruction, the predicted increase in effect size was 0.009 standard deviation units, which is considered as a small effect. These results may help health science and nursing educators by providing guidance in identifying the conditions under which various forms of innovative small-group learning pedagogies are collectively more effective than the traditional lecture-based teaching instruction.