Many colleges and universities seek to promote student success through targeted strategies for individuals or groups of students who are believed to have a higher risk of attrition. Taking a different focused approach, Supplemental Instruction (SI) provides voluntary collaborative learning sessions that are generally linked to specific undergraduate courses with a high percentage of students who either receive low grades or do not complete the course. Although a substantial body of literature has examined the outcomes associated with SI, many of these studies have notable methodological limitations, which include problems with student self-selection into SI participation. The present study examined the effects of SI using doubly robust propensity score analyses with a total of 12,641 observations from 21 different courses across 2 semesters. In both semester samples, SI participation led to higher course grades and retention. The strongest relationships were often observed for underrepresented racial minority students and for students who attended at least five SI sessions. The results did not differ systematically by students' sex, first-generation status, high school grades, and precollege standardized test scores. The findings have important implications for the use of SI to help students overcome challenges within early college coursework.