Hospital readmissions are common, expensive, and increasingly used as a metric for assessing quality of care. The relationship between index hospitalizations and specific outcomes among those readmitted remains largely unknown. Identify risk factors present during the index hospitalization associated with death or transition to hospice care during 30-day readmissions and examine the contribution of infection in readmissions resulting in death. Retrospective cohort study. A total of 17,716 30-day readmissions in an academic health system. We used mixed-effects multivariable logistic regression models to identify risk factors associated with the primary outcome, in-hospital death, or transition to hospice during 30-day readmissions. Of 17,716 30-day readmissions, 1144 readmissions resulted in death or transition to hospice care (6.5%). Risk factors identified included: age, burden, and type of comorbid conditions, recent hospitalizations, nonelective index admission type, outside hospital transfer, low discharge hemoglobin, low discharge sodium, high discharge red blood cell distribution width, and disposition to a setting other than home. Sepsis (OR=1.33; 95% CI, 1.02-1.72; P=0.03) and shock (OR=1.78; 95% CI, 1.22-2.58; P=0.002) during the index admission were associated with the primary outcome, and in-hospital mortality specifically. In patients who died, infection was the primary cause for readmission in 51.6% of readmissions after sepsis and 28.6% of readmissions after a nonsepsis hospitalization (P=0.009). We identified factors, including sepsis and shock during the index hospitalization, associated with death or transition to hospice care during readmission. Infection was frequently implicated as the cause of a readmission that ended in death.