BACKGROUND: Reactions to rituximab occur frequently, with up to 77% of patients developing a reaction during initial exposure. The safety of rechallenging patients after a reaction is not clear and standard guidelines are lacking. OBJECTIVE: To better understand clinical decision making surrounding rituximab reactions and subsequent rechallenge. METHODS: We performed a 5-year retrospective review of all rituximab reactions at a large academic outpatient infusion center. Patients' demographic characteristics, clinical symptoms, and management of reactions were reviewed. Reaction severity was classified using standard criteria. RESULTS: Between June 2006 and January 2011, 67 patients (mean age, 58 +/- 13 years, 54% men) with at least 1 rituximab reaction were identified. Most reactions occurred during the first exposure to rituximab (63%). Most reactions (n = 59 [88%]) were grade 1 or 2. Fifty-one patients (n = 51 [88%]) were rechallenged with rituximab on the same day as the initial reaction. Most patients with a grade 1 reaction tolerated rechallenge. Conversely, all 4 patients with a grade 3 reaction had a reaction during rechallenge. The outcome of same-day rechallenge after an initial grade 2 reaction was varied; most patients (26 of 31 [84%]) tolerated same-day challenge, but 5 patients had a reaction (all grade 1-2 severity). CONCLUSIONS: Consistent with previous data, our observations suggest that patients who experience grade 1 reactions to rituximab can be safely rechallenged the same day. A grade 3 or 4 reaction should prompt referral to an allergy specialist for risk assessment before additional rituximab administration. Further research is needed to understand the optimal management of patients with grade 2 reactions. (C) 2016 American Academy of Allergy, Asthma & Immunology