Background: Musculoskeletal disorders (MSDs) are common in the workplace and are a public health issue. Persistent pain despite conservative treatment or surgery may lead to poor long-term outcomes. Objective: To compare the effect of a combined 6-day program of exercise, self-management workshops and spa therapy with self-management on functional capacity in personal and professional daily life at 3 months in people with musculoskeletal disorders. Methods: We conducted a prospective, randomized controlled trial. Participants were employed (any type of work) and aged between 18 and 65 years, with latent or symptomatic upper extremity MSDs, with or without a history of sick leave. They were randomized to participate in 6 days (2 h per day) of spa therapy, exercise, and self-management workshops immediately (intervention) or at 3 months (control). The control group performed self-management until 3 months. The primary outcome was the score on the self-reported Quick Disability of Arm-Shoulder-Hand (QuickDASH) at 3 months. The primary analysis was conducted using analysis of covariance with baseline QuickDASH score as the covariate. Results: In total, 150 participants were randomized (85 % women): 78 to the control group and 72 to the intervention group. At 3 months, the QuickDASH total and work scores did not differ between groups (effectsize [ES] = -0.15, 95 %CI, -0.38 to 0.09, p = 0.215, and ES = -0.11, 95 % CI, -0.35 to 0.12, p = 0.343). However, QuickDASH sport/performing arts score was significantly different between randomization groups at 3 months (ES =-0.25, 95 % CI, -0.48 to -0.02, p = 0.035). Conclusions: This study provided no evidence in favor of a short-course, personalized self-management, intensive spa therapy intervention over self-management alone for the management of upper-extremity MSDs. Trial registration: ClinicalTrials.gov (NCT02702466) retrospectively registered.