Objectives: To estimate the rates of hospitalizations in patients within 12 months after the first rituximab administration. Methods: Patients who received rituximab between 2001 and 2008 for either benign or malignant conditions were identified from Texas Medicare files. The hospitalization rates for these patients with any diagnoses that might represent toxicity were then compared in the 12 months before and after the first infusion of rituximab. Dose-response analyses were performed on the basis of the number of doses received in the 8 weeks after initiating rituximab and also using the cumulative number of doses as a time-dependent covariate. Results: In all, 2623 patients received rituximab as a single agent for malignant indications and 1124 received it for benign indications. Overall inpatient admission rates did not differ significantly between the 12 months before and after rituximab initiation in patients with benign or malignant conditions. Those with malignant conditions had higher rates of hospitalizations for cardiovascular, infectious, pulmonary, and neurological diagnoses after rituximab initiation. In those with nonmalignant conditions, the only increase was in hospitalizations for infections. Neither group of patients showed any clear dose-response relationships with any toxicity. Conclusions: The increased hospitalizations for potential toxicities seen in patients with malignant disease were presumably because of the underlying disease process and not rituximab. Rituximab does not appear to be associated with hospitalizations for serious toxicity within 12 months after the first infusion, with the possible exception of infection.