This study aims to investigate the efficacy and safety of laparoscopic splenectomy (LS) in the management of refractory thrombocytopenia associated with systemic lupus erythematosus (SLE). From January 2003 to February 2012, 20 patients underwent splenectomy for thrombocytopenia associated with SLE. Of these, 11 underwent open (SLE-OS group) and 9 underwent laparoscopic splenectomy (SLE-LS group). Another 15 patients with ITP underwent LS (ITP-LS group) were categorized as the control group. Surgical indications, perioperative details, and short- (90 days) and long- (median, 42 months) term hematological outcomes were assessed. Splenectomy was successful in all 20 SLE patients. The mean platelet count increased from 23 × 10(9)/L before splenectomy to 289.2 × 10(9)/L and 144.2 × 10(9)/L after 3 and 6 months, respectively, and was 115.5 × 10(9)/L at the last visit, with a 3-month complete response (CR) rate of 100 %. After a median follow-up of 42 months, 17 patients (85 %) had a CR or partial response (PR) to splenectomy plus medical therapy. SLEDAI score and dosage of steroids decreased significantly after splenectomy. None of these patients experienced any postoperative infection, bleeding, or thrombotic events. SLE-LS group had lower volumes of estimated blood loss and postoperative drainage and shorter postoperative hospital stay than SLE-OS group. There were no statistically significant differences between the SLE-LS and ITP-LS groups in operation time, estimated blood loss, and postoperative hospital stay. Splenectomy is effective and safe in the management of refractory thrombocytopenia secondary to SLE. LS may be safe and effective in thrombocytopenia associated with SLE.