OBJECTIVES: Recent medical cost estimates of musculoskeletal disorders (MSDs) as a group have not been calculated. This study estimates the incremental direct medical cost for individuals with MSDs in the United States (US). METHODS: Retrospective analysis was conducted using the 2006 Medical Expenditure Panel Survey (MEPS) data. Individuals, 18 year and older were identified using International Classification of Diseases (ICD)-9 diagnosis codes 274.xx and 710.xx-739.xx for all diseases under MSDs. Incremental total expenditures of MSDs was estimated using a regression model adjusting for various factors like age, gender, geographic region, race, ethnicity, education, insurance status and number of medications(proxy measure for comorbidity). Generalized linear and regression models were built to analyze the overall incremental treatment cost of MSDs. RESULTS: Of the 105,166 individuals sampled in 2006 MEPS data, approximately 11,129 individuals (10.58%) experienced at least one MSD. Majority of the individuals were females%, whites%, and 40 years and older. The total treatment cost for MSDs was $479.19 billion in 2006 compared to $193 billion in 1996. The largest cost components in 2006 were hospitalizations, physician visits, and prescription medications. CONCLUSIONS: With incremental medical expenditures estimated at $US 479 billion, individuals with MSDs utilize significant amount of health care resources. The systematic assessment of MSDs and their associated cost is necessary to increase the awareness of MSDs prevalence in our population. There is a need for MSD-related intervention programs which can be instrumental in reducing the costly impact of MSDs on individuals’ well-being and productivity.