Small-for-size (SFS) graft syndrome is one of the major causes of graft loss in living donor liver transplantation (LDLT). We examined whether splenectomy is beneficial for overcoming SFS graft syndrome in LDLT. The patients were classified into two groups: the Sp (-) group (n=69), in which splenectomy was not performed, and the Sp (+) group (n=44), in which it was. The incidence of SFS graft syndrome was investigated. Risk factors of SFS graft syndrome were identified by univariate- and multivariate analysis. To clarify whether splenectomy is beneficial for patients with a SFS graft, subgroup analysis was performed for patients who had a graft weight-to-standard liver weight (GW-SLW) ratio of 40% or less (n=50). Thirty-one of 113 patients developed SFS graft syndrome. A multivariate analysis identified that having a male donor was an independent risk factor of SFS graft syndrome. SFS graft syndrome occurred in 11 of 50 patients with a GW-SLW ratio<40%, and Sp (-) was an independent risk factor for the occurrence of SFS graft syndrome in patients (P=0.014). Simultaneous splenectomy is favorable for overcoming SFS graft syndrome in LDLT patients with a GW-SLW of 40% or less.