Background: Musculoskeletal disorders (MSD) are the major cause of morbidity throughout the world, having a substantial influence on quality of life (QOL). We studied QOL ascertained by limitations of activities of daily living, impact on family and social relationships, and sleep disturbances among patients with MSD. Aim: Ascertain QOL in MSD. Materials and Methods: A cross-sectional study among 2633 randomly selected subjects. The study was carried out in the field practice area of D Y Patil Medical College, Pune, India. In the first phase of the study, patients of MSD were identified by house-to-house surveys, by face-toface interviews, and clinical examination carried out by trained interns in random samples of selected households. Subsequently, QOL in patients with MSD was elicited by measuring limitations of activities of daily living, impact on family and social relationships and sleep disturbances by structured instrument, using Likert/Dichotomous Scale. Statistical software EPI Info 2002 was used for estimation of sample size, data entry, and analysis. Data were summarized using proportions and percentages. Association of gender and rural–urban background with prevalence of musculoskeletal disorders was explored with odds ratio (OR) with 95% confidence intervals. Results: A total of 2633 subjects were examined. Out of these, 190 (7.2%) suffered from various types of MSD, with higher prevalence in females than males (OR=1.43, 95% CI=1.05 to 1.95). Prevalence was also higher in the rural population compared with urban (OR=2.02, 95% CI=1.45 to 2.83). However, the rural–urban difference may be due to the confounding effect of age, as prevalence was higher in the elderly (48.78%) and the mean age of the rural population was significantly higher than the urban population. Different degrees of limitations among patients of MSD in carrying out specific activities were: Dressing 9.5%, washing hair 11.6%, rising from bed 50%, feeding themselves 6%, walking 39%, taking bath 10%, toilet 37%, rising from chair 47%, rising from floor 55%, boarding bus 30%, and sleep disturbances 47%. These limitations also had impact on their family and social relationships. Conclusions: Patients of musculoskeletal disorders face appreciable limitations in their activities of daily living, which adversely impact their QOL.