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Abstract Engineering education has increasingly embraced active learning techniques within a variety of curricula. In particular, project-based active learning techniques have a significant potential to enhance students' learning experience. In this study, we implemented project-based techniques in biomedical engineering (BME) classes, and we investigated the effects of active learning on students' self-efficacy as an effective predictor of students' academic persistence and their career decision-making. Differences in self-efficacy were compared across genders. A high level of internal consistency was observed for both academic and career-oriented scales, as determined by Cronbach's alpha values of 0.908 and 0.862, respectively. While average scores of all survey questions indicated improvement in students' academic and career-oriented self-efficacy measures, significant improvements were observed in “clearer vision of programming application in engineering” and “BME careers,” as well as in “expectation of success in a future BME career that involves developing medical devices” after the completion of the project-based activity (p = 0.002, 0.023, and 0.034, respectively). For two of the survey questions, female students reflected a significantly lower “self-confidence about understanding the most complex course material” as well as a significantly lower “willingness to have a future career in BME that involves intensive computer programing” as compared to male students (p = 0.035 and 0.024, respectively). We have further discussed possible explanations for the observed differences and multiple potential ways to enhance gender equality in STEM fields from a self-efficacy standpoint.