Increasing student success and retention rates are top goals for many higher education institutions. Supplemental Instruction (SI) is a widely used academic support program designed to increase students’ academic performance and provide students the learning skills they need to persist to graduation. Unfortunately, a lack of time, personnel, and resources often prevent in-depth, meaningful analysis on the effectiveness of SI programs. This study examined the relationship of attending SI sessions for first-year chemistry courses to student grade outcomes and retention rates for attendees. The gender of SI leaders and SI participants was also assessed to determine if leader and participant gender were related to SI attendance, final course grades, or retention. The results indicated that students who attended SI earned significantly higher final course grades and were retained at significantly higher rates after one and two terms. A positive correlation was discovered between the number of SI sessions attended and final course grades. Significant differences in final grades were demonstrated between students who attended SI and those who did not at all levels of composite ACT scores. Both male and female students showed a preference for gender-matching with their SI leader, but students who attended SI sessions with both male and female SI leaders earned higher final course grades than students who gender-matched with their SI leader and students who only attended SI sessions with an SI leader whose gender differed from their own. No significant differences were found between male and female students for final course grades or retention outcomes.