BACKGROUND: Chronic musculoskeletal pain is prevalent among laboratory technicians and work-related stress may aggravate the problem. OBJECTIVES: This study investigated the effect of a multifaceted worksite intervention on pain and stress among laboratory technicians with chronic musculoskeletal pain using individually tailored physical and cognitive elements. STUDY DESIGN: This trial uses a single-blind randomized controlled design with allocation concealment in a 2-armed parallel group format among laboratory technicians. The trial "Implementation of physical exercise at the Workplace (IRMA09)--Laboratory technicians" was registered at ClinicalTrials.gov prior to participant enrolment. SETTING: The study was conducted at the head division of a large private pharmaceutical company's research and development department in Denmark. The study duration was March 2014 (baseline) to July 2014 (follow-up). METHODS: Participants (n = 112) were allocated to receive either physical, cognitive, and mindfulness group-based training (PCMT group) or a reference group (REF) for 10 weeks at the worksite. PCMT consisted of 4 major elements: 1) resistance training individually tailored to the pain affected area, 2) motor control training, 3) mindfulness, and 4) cognitive and behavioral therapy/education. Participants of the REF group were encouraged to follow ongoing company health initiatives. The predefined primary outcome measure was pain intensity (VAS scale 0-10) in average of the regions: neck, shoulder, lower and upper back, elbow, and hand at 10 week follow-up. The secondary outcome measure was stress assessed by Cohen´s perceived stress questionnaire. In addition, an explorative dose-response analysis was performed on the adherence to PCMT with pain and stress, respectively, as outcome measures. RESULTS: A significant (P < 0.0001) treatment by time interaction in pain intensity was observed with a between-group difference at follow-up of -1.0 (95%CI: -1.4 to -0.6). No significant effect on stress was observed (treatment by time P = 0.16). Exploratory analyses for each body region separately showed significant pain reductions of the neck, shoulders, upper back and lower back, as well as a tendency for hand pain. Within the PCMT group, general linear models adjusted for age, baseline pain, and stress levels showed significant associations for the change in pain with the number of physical-cognitive training sessions per week (-0.60 [95%CI -0.95 to -0.25]) and the number of mindfulness sessions (0.15 [95%CI 0.02 to 0.18]). No such associations were found with the change in stress as outcome. LIMITATIONS: Limitations of behavioral interventions include the inability to blind participants to which intervention they receive. Self-reported outcomes are a limitation as they may be influenced by placebo effects and outcome expectations. CONCLUSIONS: We observed significant reductions in chronic musculoskeletal pain following a 10-week individually adjusted multifaceted intervention with physical training emphasizing dynamic joint mobility and mindfulness coupled with fear-avoidance and de-catastrophizing behavioral therapy compared to a reference group encouraged to follow on-going company health initiatives. A higher dose of physical-cognitive training appears to facilitate pain reduction, whereas a higher dose of mindfulness appears to increase pain. Hence, combining physical training with mindfulness may not be an optimal strategy for pain reduction. TRIAL REGISTRATION: NCT02047669.