The objective of this study is to identify risk factors for permanent work disability (PWD) related to musculoskeletal disorders (MSDs). This is a secondary data analysis of a randomized controlled intervention study in Temporary Work Disability (TWD) due to MSDs. The association of PWD (claim submission and status recognition) with baseline clinical, sociodemographic, work-related administrative and occupational factors was analyzed by Cox proportional hazards models. Of 3,311 patients with TWD, 47 submitted a PWD claim, of whom 32 achieved PWD status. The main alleged causes of the PWD were back pain, sciatica, and inflammatory diseases. The following factors were independently associated with an increased probability of PWD claim submission: age (odds ratio (OR) 5.1), being woman (OR 2.1), self-employment (OR 3.4), unemployment (OR 13.8), previous musculoskeletal surgery (OR 16), repeated TWD (OR 3.4), sitting (OR 2.8), and raising arms frequently (OR 3.1). Patients with inflammatory disease were more likely to file PWD claims (OR 10.4) while tendonitis was associated with lower probability (OR 0.3). The sociodemographic factors that better predicted PWD status recognition were age (OR 5.7), low educational level (OR 4.2), previous musculoskeletal surgery (OR 14.9), unemployment (OR 17.6), sitting (OR 2.6), and raising arms frequently (OR 2.7). Inflammatory diseases were the diagnoses associated with a higher rate of PWD status recognition (OR 6.1). Inflammatory diseases have a high chronic disability potential in active workers. Sociodemographic, work-related, occupational factors, and other clinical factors, some of which are modifiable, may explain the development of long-term work disability related to MSDs.