Objectives: This review aims to evaluate the performance of serious games as a training tool compared to other methods of continued professional development (CPD) and continued medical education (CME) for healthcare professionals. Methods: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Web of Science, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), PLOS ONE, ClinicalTrials. gov, were searched for available randomized control trials (RCTs) up to June 2018. We used the CASP (Critical Appraisal Skills Programme) tool to evaluate the quality of RCTs. Results: The search identified 1430 papers; among them, 119 were evaluated. Finally 17 RCTs involving 2978 participants... were selected in this systematic review. The serious games (SGs) were classified into three broader categories: 1) specifically designed games to enhance training skills and learning gains, 2) game design elements to bolster the sense of competition for knowledge enhancement, 3) commercially available video games for training on medical procedures. Four studies found levels of satisfaction among participants of SGs to be high; none of the studies evaluated the impact of the games on beliefs or behaviors. Overall, the studies provided limited evidence to support a strong connection between the use of serious games and improved performance. Conclusion: SGs can be an effective alternate/ complementary component of healthcare training curriculum. However, existing heterogeneous assessment methodologies are not accurately depicting the effectiveness of games. More robust RCTs/research designs are needed to evaluate the effectiveness of serious games.