Background: Intraoperative bleeding is the main complication and main cause of conversion to open surgery during laparoscopic splenectomy (LS). We present the advantages of the lateral approach and the use of the ultrasonic shears (US) for achieving a safer vascular control. Methods: We have performed a total of 48 LS using several approaches. In our initial experience 10 patients underwent surgery with an anterior approach. In the second series of 18 patients, we used a manually assisted procedure. In the last 20 patients, we employed a technique with a full lateral position. Only three ports have been used. The major part of the dissection was conducted from behind, thus allowing a safer vascular control. The division of short gastric vessels and lower pole vessels was performed using US. The main vascular pedicle was stapled. The spleen was removed through a short Pfannenstiel incision. There were 9 males and 11 females with a mean age of 36 years (range, 18–71 years). Fourteen had immune thrombocytopenic purpura (ITP); two had an HIV-infection-related purpura; two had an autoimmune hemolytic anemia; and two had a spherocytosis. Results: All the 20 LS were completed. The average splenic weight was 274 g (range, 162–1,400 g). In all but one patient, the intraoperative blood loss was less than 60 ml, and was none in six patients (average, 51 ml). In our initial series of 10 patients surgically treated with an anterior approach, the average blood loss was 180 ml, and it was 230 ml in the series of hand-assisted procedures. The average operative time was 127 min (range, 70–220 min), including the time required by the change of position and the Pfannenstiel incision. There was no mortality. All but one patient had an uneventful postoperative course. The HIV-infected patient had a severe postoperative pancreatitis. In those patients with an uncomplicated course, the average postoperative stay was 4.3 days (range, 2–8 days). Conclusions: The lateral position with a posterior approach to splenic vessels allows for safe vascular control. The use of US results in a gain of time and safety. The average intraoperative bleeding of this series is much lower than that observed in our previous experience and in other published series.