A longstanding challenge facing MD-PhD students and other dual-degree medical trainees is the loss of clinical knowledge that occurs during the non-medical phases of training. Academic medical institutions nationwide have developed continued clinical training and exposure to maintain clinical competence; however, quantitative assessment of their usefulness remains largely unexplored. The current study therefore sought to both implement and optimize an online game platform to support MD-PhD students throughout their research training. Sixty-three current MD-PhD students completing the PhD research phase of training were enrolled in an institutionally developed online game platform for 2 preliminary and 4 competition rounds of 3–4 weeks each. During preliminary game rounds, we found that participation, though initially high, declined precipitously throughout the duration of each round, with 37 students participating to some extent. Daily reminders were implemented in subsequent rounds, which markedly improved player participation. Average participation in competition rounds exceeded 35% (23/63) active participants each round, with trending improvement in scores throughout the duration of PhD training. Both player participation and progress through the research phase of the MD-PhD program correlated positively with game performance and therefore knowledge retention and/or acquisition. Coupled with positive survey-based feedback from participants, our data therefore suggest that gamification is an effective tool for MD-PhD programs to combat loss of clinical knowledge during research training.