The Oklahoma IDeA Network of Biomedical Research Excellence (OK-INBRE) provides a formalized mentoring program and grant awards to new and early-stage faculty throughout Oklahoma. The OK-INBRE Research Project Investigator (RPI) award program has supported 30 faculty from both research-intensive universities and primarily undergraduate institutions (PUIs) over the past 15 yr. To examine the impact of this program, we assessed the career trajectory of OK-INBRE RPI awardees and compared their productivity with a control group of applicants who applied for but did not receive an RPI award. A mixed-methods approach was employed to assess longitudinal programmatic impact. Regression analyses were conducted to estimate the effect of an RPI award on faculty productivity, controlling for institutional affiliation. Key informant interviews were conducted to capture qualitative information about satisfaction and additional outcomes. OK-INBRE RPI awardees had a higher number in total and mean number of publications. In achieving extramural funding, RPI awardees were 12.5 times (P = 0.005) as likely to receive a grant award of any type and 4.5 times (P = 0.06) as likely to receive a subsequent federal grant as those in the control group. Many RPI awardees attributed their career success to OK-INBRE, but they also helped to identify barriers to advancement or productivity associated with their specific home institutions. The combined data indicate that OK-INBRE plays a significant role in launching new and early-stage investigators on a path toward independent research careers, which will in turn have a positive impact on the future of the biomedical research enterprise in Oklahoma.