Abstract Based on the prevalence of musculoskeletal pain in the context of interference with daily activities (IDA) and treatment for musculoskeletal disorders in the study population (n = 3188), we estimated the prevalence and years lived with disability (YLD) of musculoskeletal pain in Japan. The total of 42,287 thousand (41.2%) of Japanese adult people was estimated to suffer from musculoskeletal pain. Among them, 9127 thousand was estimated to interfere with daily activities due to the pain. Overall YLD for musculoskeletal pain in Japan were estimated at 1,297,843.7 (1263.6 per 100,000). The YLD for Pain without IDA were 33,159.3 (32.3 per 100,000) and the YLD for Pain with IDA were 1,264,684.4 (1231.3 per 100,000). One-way sensitivity analysis showed that the YLD of musculoskeletal pain might increase to 4,421,844.0 (4305.2 per 100,000) with the increased disability weight for Pain without IDA of 0.1, while they might inversely decrease to 1,018,875.0 (992.0 per 100,000) with the increased treatment rate in Pain with IDA of 100%. Musculoskeletal pain imposes a substantial burden on the Japanese adult population. To allow the population to keep their health-related quality of life, health professionals should pay more attention to musculoskeletal pain and make positive efforts to improve prevention and control of musculoskeletal pain.