Background: Microbiology is a critical and expansive topic that many medical schools’ curriculum must teach in a constrained time frame. We implemented a microbiology question bank smart phone app enhanced with game elements and clinical pearls during a microbiology course for first-year medical students. We hypothesized that these enhancements and clinical pearls would engage the students meaningfully and increase their knowledge base. Methods: Though use was optional, students’ game play was recorded through the app, which was compared to test grades retrospectively. A player efficiency rating (PER) was calculated as a function of question response, accuracy, and engagement. Students were separated into tertiles of PER and median exam grades were compared using a non-parametric Kruskal–Wallis (KW) test. An anonymous satisfaction and usability feedback survey was also administered. Results: One hundred eighty-one of the 189 students (96%) answered at least one question, and 165 (87%) completed all 56 questions. The average PER was 84.75. We received feedback surveys from 61 (34%) students in the course, with positive responses regarding the perceived impact on learning microbiology. The KW test found a positive correlation for median exam scores of the player groups when divided into tertiles by PER (p = 0.0002). Conclusions: We leveraged gamification and clinical pearls to design a supplemental microbiology question bank. We found high engagement overall and higher class exam scores associated with greater use of the question bank.