ABSTRACT: OBJECTIVES:Case volume-outcome associations bolster arguments to regionalize severe sepsis care, an approach that may necessitate interhospital patient transfers. Although transferred patients may most closely reflect care processes involved with regionalization, associations between sepsis case volume and outcomes among transferred patients are unclear. We investigated case volume-outcome associations among patients with severe sepsis transferred from another hospital. DESIGN:Serial cross-sectional study using the Nationwide Inpatient Sample. SETTING:United States nonfederal hospitals, years 2003-2011. PATIENTS:One hundred forty-one thousand seven hundred seven patients (weighted national estimate of 717,732) with severe sepsis transferred from another acute care hospital. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:We examined associations between quintiles of annual hospital severe sepsis case volume for the receiving hospital and in-hospital mortality among transferred patients with severe sepsis. Secondary outcomes included hospital length of stay and total charges. Transferred patients accounted for 13.2% of hospitalized severe sepsis cases. In-hospital mortality was 33.2%, with median length of stay 11 days (interquartile range, 5-22), and median total charge $70,722 (interquartile range, $30,591-$159,013). Patients transferred to highest volume hospitals had higher predicted mortality risk, greater number of acutely dysfunctional organs, and lower adjusted in-hospital mortality when compared with the lowest-volume hospitals (odds ratio, 0.80; 95% CI, 0.67-0.90). In stratified analysis (p < 0.001 for interaction of case volume by organ failure), mortality benefit associated with case volume was limited to patients with single organ dysfunction (n = 48,607, 34.3% of transfers) (odds ratio, 0.66; 95% CI, 0.55-0.80). Treatment at highest volume hospitals was significantly associated with shorter adjusted length of stay (incidence rate ratio, 0.86; 95% CI, 0.75-0.98) but not costs (% charge difference, 95% CI: [-]18.8, [-]37.9 to [+]0.3). CONCLUSIONS:Hospital mortality was lowest among patients with severe sepsis who were transferred to high-volume hospitals; however, case volume benefits for transferred patients may be limited to patients with lower illness severity.