- Importance: The association between hospital volume and inpatient mortality for severe sepsis is unclear. Objective: To assess the effect of severe sepsis case volume and inpatient mortality. Design Setting and Participants: Retrospective cohort study from 646,988 patient discharges with severe sepsis from 3,487 hospitals in the Nationwide Inpatient Sample from 2002 to 2011. Exposures: The exposure of interest was the mean yearly sepsis case volume per hospital divided into tertiles. Main Outcomes and Measures: Inpatient mortality. Results: Compared with the highest tertile of severe sepsis volume (>60 cases per year), the odds ratio for inpatient mortality among persons admitted to hospitals in the lowest tertile (<= 10 severe sepsis cases per year) was 1.188 (95% CI: 1.074-1.315), while the odds ratio was 1.090 (95% CI: 1.031-1.152) for patients admitted to hospitals in the middle tertile. Similarly, improved survival was seen across the tertiles with an adjusted inpatient mortality incidence of 35.81 (95% CI: 33.64-38.03) for hospitals with the lowest volume of severe sepsis cases and a drop to 32.07 (95% CI: 31.51-32.64) for hospitals with the highest volume. Conclusions and Relevance: We demonstrate an association between a higher severe sepsis case volume and decreased mortality. The need for a systems-based approach for improved outcomes may require a high volume of severely septic patients.