Laparoscopic splenectomy (LS) is gaining wide acceptance as a safe, effective alternative to open splenectomy (OS) in the treatment of hematologic disorders in adult and pediatric patients, with low conversion rates and complications. The aim of this retrospective case-control study was to compare two cohorts of patients, with similar characteristics, who underwent OS or LS in a single institution. The medical records of the initial 20 consecutive patients who underwent LS were reviewed and compared with a control group of 28 patients undergoing OS, matched for age, gender, diagnosis, splenic size and weight, and American Society of Anesthesiologists score. Data were collected regarding operative time, blood loss, blood transfusions, pathologic findings, accessory spleen detection, complications, ileus duration, and postoperative hospital stay. Nineteen patients underwent attempted LS. One procedure (5%) was converted to OS for uncontrolled hilar bleeding. Accessory spleens were detected in two cases in the LS group compared with four cases in the OS group (14%). Mean operative time was 165 minutes (range: 100-240 minutes) for LS and 114 minutes (75-180 minutes) for OS (P < 0.001). In the LS group a regular diet was tolerated 36 hours (range: 24-48 hours) after surgery compared with 72 hours (range: 48-96 hours) for the OS group (P < 0.001), and mean postoperative hospital stay was 4.1 days (range: 3-8 days) for LS, compared with 8.1 days (range: 5-12 days) for OS (P < 0.001). No differences were observed in blood loss, complication rates, or transfusion requirements. Compared with OS, LS requires more operative time (showing a learning curve), is comparable in blood loss, transfusion requirements, complication rates, and detection of accessory spleens and appears to be superior in terms of return of bowel function and hospital stay.