Of these, 22 RCTs were eventually included in the meta-analysis. Results: Of the 935 citations retrieved, 33 studies were included in this review. We used a narrative and statistical approach, as appropriate, to synthesize the results of the included studies. Two reviewers independently carried out the study selection, data extraction, risk of bias assessment, and quality of evidence appraisal. We also conducted backward and forward reference list checking for the included studies and relevant reviews. The following seven databases were searched: MEDLINE, CINAHL, PsycINFO, ACM Digital Library, IEEE Xplore, Scopus, and Google Scholar. Methods: We conducted a systematic review of randomized controlled trials (RCTs). Objective: This study aims to assess the effectiveness of serious games in alleviating anxiety by summarizing the results of previous studies and providing an up-to-date review. The effectiveness of serious games in alleviating anxiety has been investigated by several systematic reviews however, they were limited by design and methodological weaknesses. One of the nonpharmacological treatments used for reducing anxiety is serious games, which are games that have a purpose other than entertainment. JMIR Bioinformatics and Biotechnology 16 articlesÄivision of Information and Computing Technology, College of Science and EngineeringÄ®mail: Anxiety is a mental disorder characterized by apprehension, tension, uneasiness, and other related behavioral disturbances.JMIR Biomedical Engineering 59 articles.JMIR Perioperative Medicine 65 articles.Journal of Participatory Medicine 69 articles.JMIR Rehabilitation and Assistive Technologies 168 articles.JMIR Pediatrics and Parenting 224 articles.Interactive Journal of Medical Research 244 articles.JMIR Public Health and Surveillance 940 articles.Journal of Medical Internet Research 6775 articles.