Importance: As private equity (PE) acquisitions of short-term acute care hospitals (ACHs) continue, their impact on the care of medically vulnerable older adults remains largely unexplored. Objective: To investigate the association between PE acquisition of ACHs and access to care, patient outcomes, and spending among Medicare beneficiaries hospitalized with acute medical conditions. Design, Setting, and Participants: This cross-sectional study used a generalized difference-in-differences approach to compare 21 091 222 patients admitted to PE-acquired vs non-PE-acquired short-term ACHs between January 1, 2001, and December 31, 2018, at least 3 years before to 3 years after PE acquisition. The analysis was conducted between December 28, 2020, and February 1, 2022. Differences were estimated using both facility and hospital service area fixed effects. To assess the robustness of findings, regressions were reestimated after including fixed effects of patient county of origin to account for geographic differences in underlying health risks. Two subset analyses were also conducted: (1) an analysis including only hospitals in hospital referral regions with at least 1 PE acquisition and (2) an analysis stratified by participation in the Hospital Corporation of America 2006 acquisition. The study included Medicare beneficiaries 66 years and older who were hospitalized with 1 of 5 acute medical conditions: acute myocardial infarction (AMI), acute stroke, chronic obstructive pulmonary disease exacerbation, congestive heart failure exacerbation, and pneumonia. Exposures: Acquisition of hospitals by PE firms. Main Outcomes and Measures: Comorbidity burden (measured by Elixhauser comorbidity score), hospital length of stay, in-hospital mortality, 30-day mortality, 30-day readmission, and 30-day episode payments. Results: Among 21091222 total Medicare beneficiaries admitted to ACHs between 2001 and 2018, 20 431 486 patients received care at non-PE-acquired hospitals, and 659 736 received care at PE-acquired hospitals. Across all admissions, the mean (SD) age was 79.45 (7.95) years; 11727439 patients (55.6%) were male, and 4550012 patients (21.6%) had dual insurance; 2 996 560 (14.2%) patients were members of racial or ethnic minority groups, including 2 085 128 [9.9%] Black and 371 648 [1.8%] Hispanic; 18094662 patients (85.8%) were White. Overall, 3 083 760 patients (14.6%) were hospitalized with AMI, 2835777 (13.4%) with acute stroke, 3674 477 (17.4%) with chronic obstructive pulmonary disease exacerbation, 5 868 034 (27.8%) with congestive heart failure exacerbation, and 5 629 174 (26.7%) with pneumonia. Comorbidity burden decreased slightly among patients admitted with acute stroke (difference, -0.04 SDs; 95% CI, -0.004 to -0.07 SDs) at acquired hospitals compared with nonacquired hospitals but was unchanged across the other 4 conditions. Among patients with AMI, a greater decrease in in-hospital mortality was observed in PE-acquired hospitals compared with non-PE-acquired hospitals (difference, -1.14 percentage points, 95% CI, -1.86 to -0.42 percentage points). In addition, a greater decrease in 30-day mortality (difference, -1.41 percentage points; 95% CI, -2.26 to -0.56 percentage points) was found at acquired vs nonacquired hospitals. However, 30-day spending and readmission rates remained unchanged across all conditions. The extent and directionality of estimates were preserved across all robustness assessments and subset analyses. Conclusions and Relevance: In this cross-sectional study using a difference-in-differences approach, PE acquisition had no substantial association with the patient-level outcomes examined, although it was associated with a moderate improvement in mortality among Medicare beneficiaries hospitalized with AMI.