OBJECTIVES: To compare demographics, clinical characteristics, and healthcare costs and utilization between patients receiving total knee replacement (TKR) with and without muscle atrophy/weakness (MAW). METHODS: Medical and Pharmacy claims from a U.S. population with commercial or Medicare supplemental insurance were analyzed to select patients aged 50+ receiving TKR (first hospitalization as the index stay) between January 1, 2006-September 30, 2009. Three cohorts were constructed: patients with MAW medical claims in 1 year before the index stay (pre-MAW), patients with first MAW claim during or within the 12-month after the index stay (post-MAW), and patients without any MAW claim (no-MAW). Baseline demographic and clinical characteristics, and health care costs and utilization during 1 year prior to and after the index stay were assessed. Multivariate regression analyses were performed to compare health care costs incurred within 1 year after the index stay between cohorts. RESULTS: There were 46,058 Medicare (pre-MAW: 508; post-MAW: 1,939; no-MAW: 43,611) and 53,696 commercially-insured (pre-MAW: 470; post-MAW: 2,742; no-MAW: 50,484) patients included in this study. Pre- MAW patients were more likely to have any hospitalizations (Medicare: 35.4% vs. 15.7% vs. 13.2%; commercial: 24.9% vs. 10.4% vs. 9.1%) during the 1 year pre-index stay than those in the post-MAW and no-MAW cohorts (all P<0.05). The average annual health care costs for Medicare patients before the index stay were $25,335 (standard deviation [SD]: 30,047), $15,039 (SD: 21,357), and $12,547 (SD: 19,807) for pre-MAW, post-MAW, and no-MAW cohorts, respectively, and the numbers for the commercially-insured patients were $27,571 (SD: 32,761), and $13,131 (SD: 17,512) and $12,602 (SD: 17,786). Adjusting for demographic and clinical characteristics, both pre-MAW and post-MAW cohorts had significantly higher total health care costs (Medicare: $4,201 and $9,404; commercial: $2,737 and $66,640) than the no-MAW cohort (all p<0.01) over the 12-month post-index stay. CONCLUSIONS: Patients with MAW had higher health care costs after TKR than patients without.