Background: Serious games have emerged as an innovative educational strategy with the potential to significantly enhance the quality and effectiveness of cardiopulmonary resuscitation (CPR) training. Despite their promise, there remains a degree of controversy when comparing the advantages of serious games with traditional CPR training methods. This study seeks to provide a comprehensive assessment of the impact of serious games on CPR training and education by systematically analyzing the results of previous research., Objective: This study aimed to assess the effect of serious games on CPR training and education by summarizing and pooling the results of previous studies., Methods: We conducted a thorough and systematic search across 9 prominent web-based databases, encompassing the period from the inception of these databases until April 1, 2023. The databases included in our search were PubMed, Cochrane Library, Wiley Online Library, EBSCO (PsycInfo), SpringerLink, Chinese Biology Medicine Disc, Vip Journal Integration Platform, Wanfang Database, and Chinese National Knowledge Infrastructure. The studies selected adhered to the following criteria: (1) being a randomized controlled trial comparing serious games and traditional methods for CPR training; (2) having participants aged 12 years or older in CPR; (3) having an experimental group using serious games and a control group using nongame methods for CPR instruction; and (4) having outcomes including theoretical and skill assessments, compression depth, and rate. The Cochrane risk of bias assessment tool was used to evaluate the risk of bias. Data analysis was performed using RevMan (version 5.3; Cochrane Training), and mean differences (MDs) and standardized mean differences (SMDs) with 95% CIs were used to calculate continuous variables., Results: A total of 9 articles were included, involving 791 study participants, of whom 395 in the experimental group taught CPR training using serious games and 396 in the control group taught CPR training using traditional methods. The results of our meta-analysis indicate that the use of serious games in CPR training yields outcomes that are comparable in effectiveness to traditional training methods across several key areas. Specifically, serious games demonstrated equivalence to traditional formats in theory assessment (SMD -0.22, 95% CI - 0.96 to 0.51; P=.55), skill assessment (SMD -0.49, 95% CI -1.52 to 0.55; P=.36), compression depth (MD -3.17, 95% CI -0.18 to 6.53; P=.06), and compression rate (MD -0.20, 95% CI -7.29 to 6.89; P=.96)., Conclusions: In summary, serious games offer a viable and effective CPR education approach, yielding results comparable to traditional formats. This modality is a valuable addition to CPR training methodologies. However, caution is warranted in interpreting these findings due to limited controlled trials, small sample sizes, and low-quality meta-analyzed evidence., (©Pengfei Cheng, Yangxi Huang, Pengyu Yang, Haizhen Wang, Baichao Xu, Chaoran Qu, Hua Zhang. Originally published in JMIR Serious Games (https://games.jmir.org), 06.02.2024.)