Background. The purpose of this study was to compare the clinical outcomes and expense of laparoscopic splenectomy by the lateral approach with open splenectomy for the treatment of hematologic diseases. Methods. Medical records of 20 matched patients undergoing open splenectomy and lateral approach laparoscopic splenectomy were retrospectively reviewed detailing perioperative course, clinical outcome, and hospital charges. Results. Patients undergoing laparoscopic splenectomy (n = 10) experienced longer anesthesia (324 versus 176 minutes; p < 0.05) and operative times (261 versus 131 minutes; p < 0.05) than those undergoing open splenectomy (n = 10). No difference was noted in both intraoperative and postoperative packed red blood cells transfused. Laparoscopic splenectomy resulted in a shorter duration of nasogastric decompression (1.2 versus 2.6 days), more rapid resumption of normal oral intake (1.9 versus 4.4 days), and earlier hospital dismissal (3.0 versus 5.8 days). Although hospital charges were not significantly higher in the laparoscopic group ($17,071.00 versus $13,196.00; P > 0.05), operative charges were always significantly higher Conclusions. When compared with open splenectomy, lateral approach laparoscopic splenectomy allows a more rapid return of normal gastrointestinal function and shorter hospital stay. The operative expense of laparoscopic splenectomy is significantly higher; however, the overall hospital expense is not. If costs can be decreased, the lateral approach laparoscopic splenectomy will be the preferred operative approach.