Despite diagnostic and therapeutic advances, the majority of patients with splenic marginal zone lymphoma (SMZL) are still treated with splenectomy. We analyzed survival outcomes after surgery or rituximab-based systemic therapy in the Surveillance Epidemiology and End Results-Medicare database, using inverse probability of treatment weighting to minimize treatment selection bias. From the 657 recorded cases diagnosed between 2000 and 2007, with a median age of 77 years, we selected 227 eligible patients treated with splenectomy (68 %), rituximab alone (23 %), or in combination with chemotherapy (9 %) within 2 years from diagnosis. No significant difference between the groups was observed in the cumulative incidence of lymphoma-related death (LRD) at 3 years (19.6 % with systemic therapy and 17.3 % with splenectomy; hazard ratio [HR], 1.04; 95 % confidence interval [CI], 0.56-1.92; P = 0.90) or in the overall survival (HR, 1.01; 95 % CI, 0.66-1.55; P = 0.95). The 90-day mortality after splenectomy was 7.1 %. The rates of hospitalizations, infections, transfusions, and cardiovascular or thromboembolic events were higher after combination chemoimmunotherapy than after splenectomy. Conversely, there was no significant difference in most complications between groups treated with splenectomy or rituximab alone. The cumulative incidence of LRD after single-agent rituximab at 3 years was 18.7 % (95 % CI, 8.6-31.7). In conclusion, in SMZL patients over the age of 65 years, the risk of LRD and overall survival are similar with systemic therapy or splenectomy as initial therapy. Single-agent rituximab may offer the most favorable risk/benefit ratio in this population.