ObjectiveTo investigate pain reduction, physical performance, and psychological status compared between Hatha yoga and stretching exercises. DesignRandomized controlled non-inferiority trial Subjects150 sedentary office workers with mild/moderate neck/shoulder pain. InterventionsParticipants received group Hatha yoga or stretching exercise once a week (30 min for 4 weeks), and were asked to practice at home. Subjects were followed up at 4 and 8 weeks. Main outcome measuresThe primary outcome was a numeric rating scale (NRS) score. The secondary outcomes were a sit-and-reach test, Functional Reach Test, Neck Disability Index, pain pressure threshold, Patient Health Questionnaire-9, General Anxiety Disorder-7, and the EuroQoL. ResultsOf the 150 subjects, 59 and 71 participants in the Hatha yoga and stretching groups were analyzed. At baseline, no significant differences between groups were found. After 4 weeks, the mean difference in the NRS score was statistically significant between groups (p < 0.001), including a 95% confidence level of < 1 score, but there was no significant difference between groups for any other outcome. Most participants reported being satisfied with their assigned treatment (98.3–100%), and rated themselves as improved or much improved (91.8–98.3%) (both p > 0.05 between groups). The most common adverse events were musculoskeletal pain and muscle tension. Repeated measures analysis of variance that compared among weeks 0, 4, and 8 revealed no significant difference between groups. ConclusionHatha yoga was tentatively found to be non-inferior to stretching exercise relative to safety, for decreasing pain, anxiety, and depression, and for improving flexibility, neck functions, and quality of life.