Introduction: Exercise through video or virtual reality games (i.e. exergames) has grown in popularity among older adults; however, there is limited evidence on efficacy of exergaming on well-being related to health in this population. This systematic review examined the effectiveness of exergaming on health-related quality of life in older adults. Methods: PRISMA guidelines for this systematic review. Several databases were searched using keywords to identify peer-reviewed journal articles in English. Randomized control trials that evaluated the effect of exergaming on health-related quality of life in older adults when compared to a control group and published between January 2007 to May 2017 were included. Results: Nine articles that in total included 614 older adults with varying levels of disability, mean age 73.6 + 7.9 years old, and 67% female were analyzed. Significant improvements in health-related quality of life of older adults engaged in exergaming were reported in three studies. Sample sizes were small in 7 of the studies (N < 60). The study participants, exergaming platforms, health-related quality of life instruments, study settings and length, duration and frequency of exergaming varied across studies. Conclusion: Exergaming is a new emerging form of exercise that is popular among older adults. However, findings from this analysis were not strong enough to warrant recommendation due to the small sample sizes and heterogeneity in the study participants, exergaming platforms, health-related quality of life instruments, length, duration and frequency of the intervention and study settings. Further research is needed with larger sample sizes and less heterogeneity to adequately explore the true effects of exergaming on health-related quality of life of older adults.