Background: There is a lack of accurate information on the prevalence and causes of musculoskeletal impairment (MSI) in low income countries. The WHO prevalence estimate does not help plan services for specific national income levels or countries. In view of this, we wished to undertake a national cluster randomized survey of musculoskeletal impairment in Malawi, one of the UN Least Developed Countries (LDC), that involved a reliable sampling methodology with a case definition and diagnostic criteria that could clearly be related to the classification system used in the WHO International Classification of Functioning, Disability and Health (ICF) Methods: We selected clusters across the whole country through probability proportional to size sampling with an urban/rural and demographic split that matched the distribution of the population. Data collection was carried out from 1st July to 30th August 2016. All MSI cases were examined in more detail by medical students under supervision, using a standardized interview and examination protocol. Results: 8,801 individuals were enumerated in 1,481 households. Of the 8,548 participants that were screened and examined (response rate of 97·1%), 810 cases of MSI were diagnosed, 18% (108) mild, 54% (329) moderate and 28% (167) severe MSI as classified by ICF. There was an overall prevalence of MSI of 9·5% (CI 8·9–10·1). The prevalence of MSI increased with age, and was similar in men (9·3%) and women (96%). People without formal education were more likely to have MSI [133% (CI 11·8-14·8)] compared to those with formal education levels [8·9% (CI 8·1-9·7), p<0·001] for primary school and [5·9% (4·6-7·2), p<0·001] for secondary school. MSI had a profound impact on quality of life. Analysis of disaggregated quality of life measures using EQ-5D showed clear correlation with the ICF class. A large proportion of patients with moderate and severe MSI were confined to bed, unable to wash or undress or unable to perform usual daily activities. Overall, 33·2% of MSIs were due to congenital causes, 25·6% were neurological in origin, 19·2% due to acquired non-traumatic non-infective causes, 16·8% due to trauma and 5·2% due to infection. Extrapolation of these findings indicated that there are approximately one million cases of MSI in Malawi that need further treatment. Conclusion: This study has uncovered a high prevalence of MSI in Malawi and its profound impact on a large proportion of the population. These findings suggest that MSI places a considerable strain on social and financial structures in this low-income country. The huge burden of musculoskeletal impairment in Malawi is mostly unattended, revealing an urgent need to scale up surgical and rehabilitation services in the country.Funding Statement: : This study was funded by Norad through the Norhed programme.Declaration of Interests: The authors stated: "None declared."Ethics Approval Statement: The approval to conduct this survey was granted by the College of Medicine Research and Ethics Committee (COMREC) and The Regional Committee for Medical and Health Research Ethics (REC Western Norway) in Norway. Consent to survey the districts and clusters were granted respectively by the District Commissioner and village head for each visited district and cluster.