Objectives: Impediments due to complaints of non-traumatic arm, neck and/or shoulder (CANS) during work often leads to consultation in primary care. This study examines the occurrence of sick leave among workers with new CANS, and evaluates sick leave trajectories and their characteristics. Methods This prospective 2-year cohort study included workers with a new CANS presenting in general practice. Participants filled out postal questionnaires on sick leave at 6-monthly intervals. Latent class growth mixture modelling was used to identify distinct trajectories of sick leave. Multinomial regression analyses identified characteristics of the subgroups. Results During follow-up, of the 533 participants 190 reported at least one episode of sick leave due to CANS. Three sick leave trajectories were distinguished: (1) 'low-risk' trajectory (n=366), with a constant low probability over time; (2) 'intermediate risk' trajectory, with a high probability at first consultation followed by a steep decrease in probability of sick leave (n=122); (3) 'high-risk' trajectory (n=45), with a constant high probability of sick leave. Compared to the 'low-risk' trajectory, the other trajectories were characterised by more functional limitations, less specific diagnoses, more work-related symptoms and low coworker support. Specific for the 'high-risk' subgroup were more recurrent symptoms, more musculoskeletal comorbidity, high score on somatisation and low score on job demands. Conclusions Three trajectories of sick leave were distinguished, graded from favourable to unfavourable. Several complaint-related and work-related factors and somatisation contributed modestly to identify an unfavourable trajectory of sick leave when presenting in primary care with CANS.