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Although recent studies have shown that 30-day readmissions following sepsis are common, the overall fiscal impact of these rehospitalizations and their variability between hospitals relative to other high-risk conditions, such as congestive heart failure and acute myocardial infarction, are unknown. The objectives of this study were to characterize the frequency, cost, patient-level risk factors, and hospital-level variation in 30-day readmissions following sepsis compared with congestive heart failure and acute myocardial infarction.A retrospective cohort analysis of hospitalizations from 2009 to 2011.All acute care, nonfederal hospitals in California.Hospitalizations for sepsis (n = 240,198), congestive heart failure (n = 193,153), and acute myocardial infarction (n = 105,684) identified by administrative discharge codes.None.The primary outcomes were the frequency and cost of all-cause 30-day readmissions following hospitalization for sepsis compared with congestive heart failure and acute myocardial infarction. Variability in predicted readmission rates between hospitals was calculated using mixed-effects logistic regression analysis. The all-cause 30-day readmission rates were 20.4%, 23.6%, and 17.7% for sepsis, congestive heart failure, and acute myocardial infarction, respectively. The estimated annual costs of 30-day readmissions in the state of California during the study period were $500 million/yr for sepsis, $229 million/yr for congestive heart failure, and $142 million/yr for acute myocardial infarction. The risk- and reliability-adjusted readmission rates across hospitals ranged from 11.0% to 39.8% (median, 19.9%; interquartile range, 16.1–26.0%) for sepsis, 11.3% to 38.4% (median, 22.9%; interquartile range, 19.2–26.6%) for congestive heart failure, and 3.6% to 40.8% (median, 17.0%; interquartile range, 12.2–20.0%) for acute myocardial infarction. Patient-level factors associated with higher odds of 30-day readmission following sepsis included younger age, male gender, Black or Native American race, a higher burden of medical comorbidities, urban residence, and lower income.Sepsis is a leading contributor to excess healthcare costs due to hospital readmissions. Interventions at clinical and policy levels should prioritize identifying effective strategies to reduce sepsis readmissions.