This study investigated the relation between working conditions, in terms of physical and psychological demand, and upper-limb and neck musculoskeletal disorders (ULNMD) in female staff working in direct contact with the elderly in nursing homes. A cross-sectional survey was conducted in 105 nursing homes in France. Data on nursing-home working conditions were collected by questionnaire from occupational physicians and by self-administered questionnaire from staff. Psychosocial demand at work was assessed on Siegrist's questionnaire and ULNMD on the Nordic questionnaire. 2,328 employees were included: 628 housekeepers, 1,372 nursing assistants and 328 nurses. During the previous 12 months, 50% of the subjects (1,160) had presented with a musculoskeletal complaint concerning the neck, 38% (881) the shoulders, 10% (246) the elbows and 22% (520) the wrists. 9% (219) reported effort/reward imbalance on the 2004 Siegrist questionnaire and 42% were in a situation of over-commitment. ULNMD complaints were associated not only with physical occupational factors but also with psychosocial factors (effort/reward imbalance and over-commitment), both before and after adjustment on individual and occupational factors. Prospective studies are needed to clarify the causal role of occupational, including, organizational, psychosocial factors in ULNMD outcomes. Preventive approaches should take account of both physical and psychosocial occupational factors.