Given limited funding for school-based science education, non-school-based programs have been developed at colleges and universities to increase the number of students entering science- and health-related careers and address critical workforce needs. However, few evaluations of such programs have been conducted. We report the design and methods of a controlled trial to evaluate the Stanford Medical Youth Science Program's Summer Residential Program (SRP), a 25-year-old university-based biomedical pipeline program. This 5-year matched cohort study uses an annual survey to assess educational and career outcomes among four cohorts of students who participate in the SRP and a matched comparison group of applicants who were not chosen to participate in the SRP. Matching on sociodemographic and academic background allows control for potential confounding. This design enables the testing of whether the SRP has an independent effect on educational- and career-related outcomes above and beyond the effects of other factors such as gender, ethnicity, socioeconomic background, and pre-intervention academic preparation. The results will help determine which curriculum components contribute most to successful outcomes and which students benefit most. After 4 years of follow-up, the results demonstrate high response rates from SRP participants and the comparison group with completion rates near 90%, similar response rates by gender and ethnicity, and little attrition with each additional year of follow-up. This design and methods can potentially be replicated to evaluate and improve other biomedical pipeline programs, which are increasingly important for equipping more students for science- and health-related careers.