Exergames can provide encouraging exercise options. Currently, there is limited evidence regarding home-based exergaming in the postoperative phase of total knee replacement (TKR). This study aimed to investigate the effects of a 4-month postoperative home-based exergame intervention with an 8-month follow-up on physical function and symptoms among older persons undergoing TKR compared with home exercise using a standard protocol. In addition, a concurrent embedded design of a mixed methods study was used by including a qualitative component within a quantitative study of exergame effects. This was a dual-center, nonblinded, two-arm, parallel group randomized controlled trial with an embedded qualitative approach. This study aimed to recruit 100 patients who underwent their first unilateral TKR (aged 60-75 years). Participants were randomized to the exergame or standard home exercise arms. Participants followed a custom-made exergame program independently at their homes daily for 4 months. The primary outcomes at 4 months were function and pain related to the knee using the Oxford Knee Score questionnaire and mobility using the Timed Up and Go test. Other outcomes, in addition to physical function, symptoms, and disability, were game user experience, exercise adherence, physical activity, and satisfaction with the operated knee. Assessments were performed at the preoperative baseline and at 2, 4, and 12 months postoperatively. Exergame adherence was followed from game computers and using a structured diary. Self-reported standard exercise was followed for 4 months of intervention and physical activity was followed for 12 months using a structured diary. Qualitative data on patients' perspectives on rehabilitation and exergames were collected through laddering interviews at 4 and 12 months. This study was funded in 2018. Data collection began in 2019 and was completed in January 2022. The COVID-19 pandemic caused an unavoidable situation in the study for recruitment, data collection, and statistical analysis. As of November 2020, a total of 52 participants had been enrolled in the study. Primary results are expected to be published by the end of 2022. Our study provides new knowledge on the effects of postoperative exergame intervention among older patients with TKR. In addition, this study provides a new understanding of gamified postoperative rehabilitation, home exercise adherence, physical function, and physical activity among older adults undergoing TKR. ClinicalTrials.gov NCT03717727; https://clinicaltrials.gov/ct2/show/NCT03717727. RR1-10.2196/38434.