Studies on the effectiveness of clickers in undergraduate chemistry courses are mixed, and there is disagreement on how to effectively leverage clickers to improve student learning performance. To fill a gap in the research, we analyzed three different teaching strategies (two involving clickers) in a General Chemistry I course over a 13-year time period. Student performance outcomes (e.g., midterm exam scores, final exam grades, final course grades, and course drop rates) were analyzed from 1,551 undergraduate chemistry students from three groups: (a) students who learned through traditional lecture without clickers; (b) students who used clickers in unstructured learning environments (unassigned groups) within a traditional lecture; and (c) students who used clickers in a structured, collaborative, small-group format (assigned groups) to solve problems during lecture. ANOVA indicated a statistically significant difference between Group 1 (lecture without clickers) and Group 3 (clickers in conjunction with collaborative, small, assigned groups) on all student performance outcomes studied. We also observed a reduction in the percentage of students withdrawing from the course when comparing the traditional lecture group to the groups exposed to clickers.