Background: Despite advances in diagnosis and therapy, over 50% of patients with splenic marginal zone lymphoma (SMZL) undergo splenectomy. The objective of this retrospective study was to compare outcomes in SMZL patients undergoing surgery or rituximab-containing chemoimmunotherapy (RCIT) based on the Surveillance, Epidemiology, and End Results-Medicare linked database. Methods: Records of 521 SMZL patients diagnosed between 2000 and 2007 were extracted, excluding cases with incomplete Medicare coverage. Two treatment arms were defined by receipt of RCIT or splenectomy within 2 years of diagnosis. Factors confounding treatment selection or prognosis were balanced in both arms using a propensity score. The primary endpoint was lymphoma-related death, estimated using competing risk models, with overall survival (OS) and toxicities as secondary endpoints. Results: Of the 341 eligible patients (median age, 77 years), 67 (20%) were untreated, while 169 (50%) underwent splenectomy and 97 (28%) chemotherapy (64% single-agent rituximab) at median 1.4 months from diagnosis. Stage IE, treatment in a teaching hospital and good performance status were associated with a preference for splenectomy. There was no evidence of significantly different risk of lymphoma-related death after treatment with RCIT rather than surgery (hazard ratio, HR, 1.10, 95%CI 0.56-2.18, P=0.78). There was an excess of early mortality after splenectomy (7% within 90 days) but more later events with RCIT (OS at 3 years 69% vs. 67%, respectively). More patients required chemotherapy after surgery (38%) than vice versa (14%, P<0.001). Nursing home admissions were more common after splenectomy (22%, P=0.03). There were more inpatient hospitalizations after multidrug RCIT (P=0.003), but not after rituximab alone (P=0.65). Conclusions: Although SMZL is considered indolent, most elderly patients required treatment soon after diagnosis in this population-based study. Survival outcomes were similar after either RCIT or splenectomy. Complications of surgery or combination chemotherapy are significant, suggesting rituximab alone as a more suitable option in elderly patients.