Incidence of musculoskeletal disorders (MSDs) is high among health care workers (HCWs). To determine whether MSDs are associated with preexisting anxiety and/or depression, a case-control study was carried out in female HCWs (56 cases/55 controls). Cases were HCWs with a first-time clinical diagnosis of MSD within the previous 2 years. Occupation, workplace, work shift, direct patient assistance, and anxiety/depression scores (Goldberg scale) were assessed. Increased risk of incident MSDs (multivariate logistic regression) was found in workers with preexisting anxiety/depression compared to those without (OR 5.01; 95% CI 2.20–12.05; p < .01). Other significant risk factors were direct patient assistance (OR 2.59; 95% CI 1.03–6.92; p = .04) and morning work shift (OR 2.47; 95% CI 0.99–6.48; p = .05). Preexisting anxiety/depression was associated with incident MSDs in HCWs, adjusting for occupational exposure risk factors.