BACKGROUND: Workplace yoga improves the physical and mental health of white-collar workers. PRIMARY STUDY OBJECTIVE: To compare the effects of yoga practiced synchronously or asynchronously on stress level, fatigue, sleep quality, work efficiency, musculoskeletal disorders, and quality of life in white-collar workers. METHODS: A randomized controlled trial. SETTING: Digital platform. PARTICIPANTS: Twenty-two workers were randomized into synchronous or asynchronous groups. INTERVENTION: Both groups were enrolled in a yoga program for eight weeks, three days a week, and for 40-45 minutes per session. While the synchronous group participated in the yoga program via Zoom video conference, the asynchronous group followed the YouTube videos for instructions. PRIMARY OUTCOME MEASURES: Stress level was evaluated with Perceived Stress Scale (PSS), fatigue with Fatigue Severity Scale (FSS), sleep quality with Pittsburgh Sleep Quality Index, work efficiency with Endicott Productivity at Work Scale, musculoskeletal disorders with Nordic Musculoskeletal Questionnaire, and quality of life with 36-Item Short Form Survey (SF-36). RESULTS: A significant decrease in FSS scores and an increase in SF-36 physical function, SF-36 mental health, and SF-36 general health perception sub-dimension scores were found in both groups (P < .05). In the synchronous group, there was a significant decrease in PSS and SF-36 pain scores, with an increase in SF-36 energy scores (P < .05). In the asynchronous group, SF-36 physical role difficulty and SF-36 social functioning scores increased (P < .05). The changes in FSS (P = .018) and SF-36 pain scores (P = .048) were significantly higher in the synchronous group. CONCLUSION: Yoga practiced synchronously or asynchronously can effectively increase the quality of life in white-collar workers. Synchronous yoga can be recommended to improve fatigue and pain-related quality of life.