Nearly 70% of US-trained doctorates in the biomedical sciences enter postdoctoral training, yet only 21% of biomedical postdoctoral scholars (postdocs) are estimated to achieve tenured or tenure-track faculty positions. Thus, there is a need to better understand the career intention patterns of postdocs and the factors that influence disparate career goals, especially for women and underrepresented minorities (URM). Based on psychosocial theories for career development and motivation, this study examines the career goals of over 1300 biomedical postdoctoral researchers and the factors that influence commitment to or divergence from conventional academic research careers. We report decreases in the number of postdoctoral researchers’ intending to pursue careers in academia only in the first two years of training. Those postdocs who are pursuing careers outside of academia have fewer publications, lower first-author publication rates, lower research self-efficacy, and different career expectations and values than those opting for research careers in academia. We found that 34% of even the most productive postdocs opt out of academia, citing expectations about job prospects and financial security. We also found that female and URM postdocs reported lower publication rates. Interestingly, female postdocs on average had lower self-efficacy than males, while URM postdocs were found to have higher self-efficacy than non-URM postdocs. Many of the postdocs who felt most comfortable choosing academic careers cited adequate support with family and childcare, financial stability, and geographical flexibility. We propose a model whereby motivations for academic careers are strengthened or weakened through self-efficacy, outcome expectations, and values during the postdoctoral training period, resulting in career goal persistence or the changing of a career intention. The results from this study help to advance our understanding of why postdocs are motivated to persist toward a career goal against considerable odds.