Rationale: Processes of care are potential determinants of outcomes in patients with severe sepsis. Whether hospitals with more experience caring for patients with severe sepsis also have improved outcomes is unclear.Objectives: To determine associations between hospital severe sepsis caseload and outcomes.Methods: We analyzed data from U.S. academic hospitals provided through University HealthSystem Consortium. We used University HealthSystem Consortium's sepsis mortality model (c-statistic, 0.826) for risk adjustment. Validated International Classification of Disease, 9th Edition, Clinical Modification algorithms were used to identify hospital severe sepsis case volume. Associations between risk-adjusted severe sepsis case volume and mortality, length of stay, and costs were analyzed using spline regression and analysis of covariance.Measurements and Main Results: We identified 56,997 patients with severe sepsis admitted to 124 U.S. academic hospitals during 2011. Hospitals admitted 460 6 216 patients with severe sepsis, with median length of stay 12.5 days (interquartile range, 11.1-14.2), median direct costs $26,304 (interquartile range, $21,900-$32,090), and average hospital mortality 25.6 6 5.3%. Higher severe sepsis case volume was associated with lower unadjusted severe sepsis mortality (R 2 = 0.10, P = 0.01) and risk-adjusted severe sepsis mortality (R 2 = 0.21, P , 0.001). After further adjustment for geographic region, number of beds, and long-term acute care referrals, hospitals in the highest severe sepsis case volume quartile had an absolute 7% (95% confidence interval, 2.4-11.6%) lower hospital mortality than hospitals in the lowest quartile. We did not identify associations between case volume and resource use.Conclusions: Academic hospitals with higher severe sepsis case volume have lower severe sepsis hospital mortality without higher costs.