Myofascial pain syndrome (MPS) is a common cause of non-articular musculoskeletal pain. The aim of this study was to estimate the prevalence and to describe the clinical features and outcome of treatment of MPS among persons with Work Related Musculoskeletal Disorders (WRMSD). A retrospective study was conducted among 20,500 clients diagnosed with WRMSD, with a mean age of 33 ± 3 years. The relevant clinical data were extracted from the treatment chart of WRMSD patients who received treatment at a tertiary level Rehabilitation Centre or on-site Occupational Health Clinics. All the clients received a sequenced, multidisciplinary treatment protocol incorporating manual therapy techniques including trigger point therapy, muscle energy technique, myofascial release, psychological approaches, yoga, exercises and ergonomic modifications. Eighty-seven percent of participants were diagnosed to have MPS. The commonest region affected was the upper back (54%), followed by the low back (44%). 76% were male and 56% worked for 8–12 hours. The commonest job categories of the participants were Managerial (33%), Software Engineers (32%) and Application Engineers (14%). Prolonged sitting, lack of rest breaks, lack of tray for keyboard and mouse, and poor posture was found to be the commonest risk factor. Associated co-morbidities were Hypovitaminosis D (26%), Hypermobile joints (24%), Osteopaenia/Osteoporosis (14%), Hypothyroidism (6%) and Hyperuricemia (6%). The commonest symptoms were Regional pain (78%), Stiffness (58%), Generalised pain (40%), Weakness (38%), Disturbed Sleep (38%), Fatigue (32%), Tingling (20%) and Numbness (18%). There was a significant reduction (P < 0.05) in pain following the rehabilitation. 95% of the subjects made a complete recovery and returned to their regular work. In view of the high prevalence of MPS in this study, healthcare professionals dealing with musculoskeletal pain need to be trained in the current approaches to diagnose and manage MPS. A comprehensive, protocol-based multidisciplinary approach is recommended for the successful management of MPS.