Importance Hospital prices are currently not subject to regulation, yet have profound financial implications for patients, taxpayers, and governments. While significant for the contemporary era of value-based care, US national variation in hospital price markup has not been delineated. Objective To characterize national variation in the hospital price markup for major elective operations and to assess the association of markup with perioperative outcomes and overall quality of care. Design, Setting, and Participants This national cross-sectional study evaluated institutional markup ratios (MRs) across 1960 US hospitals performing 4 major elective operations (abdominal aortic aneurysm repair, colectomy, coronary artery bypass grafting, and hip replacement) among patients aged 18 years and older within the 2022 Nationwide Readmissions Database. MR was defined as the ratio of charges to costs. Centers with MRs in the top decile were considered high-markup hospitals (HMH), with others categorized as non-HMH. Data were analyzed from September 2024 to March 2025. Main Outcome and Measure The primary outcome was institutional MR, with secondary consideration of perioperative outcomes. Results Of 1960 unique institutions, 194 were HMH. The median (IQR) hospital price markup factor was 3.0 (1.9-4.4). Considering only HMH, the median (IQR) MR was 8.5 (7.1-10.8); the top 50 most expensive hospitals marked up the true costs of care by a median factor of 13. On average, HMH were more commonly investor-owned, for-profit hospitals located in metropolitan areas. Of 362 367 patients, 42 620 (11.8%) were treated at HMH. Overall mean (SD) patient age was 65.1 (12.7) years, and 174 067 patients (48.0%) were female. Following risk adjustment, care at HMH was associated with significantly greater odds of major morbidity (adjusted odds ratio [AOR], 1.45; 95% CI, 1.14-1.84), including higher adjusted risk of cardiac, respiratory, infectious, and kidney sequelae. Moreover, treatment at HMH was associated with increased likelihood of nonelective readmission within 30 days (AOR, 1.33; 95% CI, 1.24-1.42). Conclusions and Relevance This cross-sectional study found that considerable variation in price markup exists across hospitals and that HMHs demonstrated both lower quality and value of care. These findings underscore that HMHs represent a key initial target for national policy efforts targeting pricing regulation, transparency, and quality improvement.