BACKGROUND: The volume-outcome relationship in patients with severe Coronavirus disease 2019 (COVID-19) is unclear and is important for establishing a system for the medical care of severe COVID-19. This study aimed to evaluate the association between institutional case volume and outcomes in patients with ventilated COVID-19. METHODS: We analyzed patients with severe COVID-19 on ventilatory control aged > 17 years who were enrolled in the J-RECOVER study, which is a retrospective multicenter observational study conducted between January 2020 and September 2020 in Japan. Based on the ventilated COVID-19 case volume, the higher one-third of institutions were defined as high-volume centers, the middle one-third as middle-volume centers, and the lower one-third as low-volume centers. The primary outcome measure was in-hospital mortality during hospitalization due to COVID-19. Multivariate logistic regression analysis for in-hospital mortality and ventilated COVID-19 case volume was performed after adjusting for multiple propensity scores and in-hospital variables. To estimate the multiple propensity score, we fitted a multinomial logistic regression model, which fell into one of the three groups based on patient demographics and prehospital factors. RESULTS: We analyzed 561 patients who required ventilator management. In total, 159, 210, and 192 patients were admitted to low-volume (36 institutions, < 11 severe COVID-19 cases per institution during the study period), middle-volume (14 institutions, 11-25 severe cases per institution), and high-volume (5 institutions, > 25 severe cases per institution) centers, respectively. After adjustment for multiple propensity scores and in-hospital variables, admission to middle- and high-volume centers was not significantly associated with in-hospital death compared with admission to low-volume centers (adjusted odds ratio, 0.77 [95% confidence interval (CI): 0.46-1.29] and adjusted odds ratio, 0.76 [95% CI: 0.44-1.33], respectively). CONCLUSIONS: There may be no significant relationship between institutional case volume and in-hospital mortality in patients with ventilated COVID-19.