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A volume-outcome relationship in ICU patients has been suggested in recent studies. However, it is unclear whether the ICU-to-hospital bed ratio affects the volume-outcome relationship. The aim of this study is to investigate the relationship between hospital volume and in-hospital mortality of adult ICU patients in relation to the ratio of ICU beds to regular hospital beds.Retrospective cohort study.Four hundred seventy-seven Japanese hospitals from 2007 to 2012 in the Japanese Diagnosis Procedure Combination database.A total of 596,143 patients discharged from acute care hospitals.None.We analyzed data from 596,143 ICU patients from 2007 through 2012 using a nationwide administrative database. Patients were categorized into nine subgroups (the tertiles of hospital volume of ICU patients combined with the tertiles of ICU-to-hospital bed ratio). Multivariable logistic regression analyses were performed to examine the concurrent effects of hospital volume of ICU patients and ICU-to-hospital bed ratio on in-hospital mortality, with adjustment for patient and hospital characteristics. Higher hospital volume of ICU patients and a higher ICU-to-hospital bed ratio were independently associated with lower mortality. When patients were stratified by ICU-to-hospital bed ratio categories, in-hospital mortality was significantly lower in the high-volume subgroup (odds ratio, 0.74; 95% CI, 0.58–0.93) compared with the low-volume subgroup in hospitals with a high ICU-to-hospital bed ratio. However, these relationships were not significant in hospitals with low ICU-to-hospital bed ratios (odds ratio, 0.94; 95% CI, 0.59–1.50) or in hospitals with intermediate ICU-to-hospital bed ratios (odds ratio, 0.80; 95% CI, 0.71–1.08).An inverse relationship between hospital volume of ICU patients and mortality was seen only when the ICU-to-hospital bed ratio was sufficiently high. Regionalization and increasing the number of ICU beds in referral centers may improve patient outcomes.