Simultaneous splenectomy (SPX) is preferentially performed in living donor liver transplantation (LDLT) to modulate portal flow; increase postoperative platelet count, especially among those with hepatitis C virus (HCV) infection; and modulate the immunologic status in ABO-incompatible cases. The negative effects of the procedure, however, are not well established. Records of 395 LDLTs performed at our institution, including 169 (42.8%) patients with simultaneous SPX and 226 (57.2%) patients with spleen preservation, were reviewed with special reference to the simultaneous SPX cases. The most common indication for SPX was HCV-related disease (n = 114), followed by low preoperative platelet count (n = 52), and other reasons (n = 3). Simultaneous splenectomy did not increase the platelet count in the early postoperative period, but the incidence of reoperation for postoperative hemorrhage was increased, mainly at the SPX site, within the first week. In addition, the operative time, intraoperative blood loss, and incidence of lethal infectious disease were significantly higher in the SPX group, whereas the incidence of small-for-size syndrome was comparable between groups. Finally, SPX was an independent predictor for both postoperative hemorrhage (odds ratio [OR] = 2.451; 95% confidence interval [CI] = 1.285-4.815; P = 0.006) and lethal infectious complication (OR = 3.748; 95% CI = 1.148-14.001; P = 0.03). In conclusion, on the basis of the present findings, we do not recommend simultaneous SPX in LDLT. Liver Transplantation 22 1526-1535 2016 AASLD.