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Inpatient Cost of Complications after Total Hip and Knee Arthroplasty. BACKGROUND: More than 1 million hip and knee total joint arthroplasties (THAs and TKAs) are performed annually in the United States. While major perioperative complications are relatively uncommon, they may substantially increase healthcare expenditures. The economic impact of individual complications, however, remains poorly defined. This study aimed to assess the effect of major complications on hospital costs and length of stay (LOS). METHODS: This study analyzed data from 2,361,402 THA/TKA patients in the Premier Healthcare claims database (2006 to 2022). The exposure was the occurrence of major postoperative complications ( e.g. , cardiac, pulmonary, renal, gastrointestinal, infectious, central nervous system, and thromboembolic complications), evaluated individually and in clusters (two coinciding or three or more coinciding). The primary outcome was total cost of hospital stay. Generalized estimating equation models compared costs across groups, reported as percent change with 95% CI. RESULTS: Median costs without complications were $16,802 (interquartile range [IQR], $13,731 to $20,838) for TKA and $17,250 (IQR, $14,072 to $21,355) for THA. In TKA, the highest costs occurred with three or more complications ($35,477; IQR, $26,078 to $52,071), sepsis ($30,633; IQR, $21,748 to $44,530), and myocardial infarction ($28,908; IQR, $21,805 to $38,744). Multivariable models confirmed the greatest adjusted increases with 3 or more complications (+136%), sepsis (+88%), and myocardial infarction (+73%) at the patient level. Frequent complications such as renal failure (+26%), pulmonary complications (+23%), and intensive care unit admission (+61%) emerged as leading drivers of overall costs. LOS accounted for a substantial share of additional costs. CONCLUSIONS: In this large national cohort, perioperative complications substantially increased hospital costs, largely via prolonged LOS. Although sepsis, stroke, and myocardial infarction were most expensive per case, the overall healthcare burden was driven by frequent complications and resource use, including intensive care unit admission, acute renal failure, pulmonary complications, mechanical ventilation, and concurrent complications. These findings suggest that targeting frequent complications and resource intensive care processes may yield the greatest impact on reducing hospital expenditures in arthroplasty surgery.