To evaluate the effects of intermittent hepatic inflow occlusion (IHIO) during donor hepatectomy for living donor liver transplantation (LDLT) in recipients and donors, we performed a single‐center, open‐label, prospective, parallel, randomized controlled study. Adult donor‐recipient pairs undergoing LDLT with right hemiliver grafts were randomized into IHIO and control groups (1:1). In the IHIO group, IHIO was performed during donor hepatectomy. The primary endpoint was the peak serum alanine aminotransferase (ALT) concentration in the recipients within 5 days after the operation. Blood samples for measurements of interleukin‐6 (IL‐6), IL‐8, tumor necrosis factor α (TNF‐α), and hepatocyte growth factor (HGF) were taken from the donors and the recipients during the operation and postoperatively. Biopsy samples for measurements of caspase‐3 and malondialdehyde (MDA) were taken from the donors and the recipients. In all, 50 donor‐recipient pairs (ie, 25 pairs in each group) completed this study. The mean peak serum ALT levels within 5 days after the operation did not differ in the recipients between the 2 groups (P = 0.32) but were higher in the donors of the IHIO group (P = 0.002). There were no differences in the prothrombin times or total bilirubin levels in the recipients or donors between the 2 groups. The amount of blood loss during donor hepatectomy was significantly lower in the IHIO group versus the control group (P = 0.02). The mean hospital stay for donors was 19.3 ± 7.2 days in the control group and 15.8 ± 4.6 days in the IHIO group (P = 0.046). There were no in‐hospital deaths within 1 month and no cases of primary nonfunction or initially poor function in the 2 groups. The concentrations of IL‐6, IL‐8, TNF‐α, and HGF did not differ between the 2 groups, nor did the concentrations of caspase‐3 and MDA. In conclusion, although we found differences in postoperative peak serum ALT levels in donors, donor hepatectomy with IHIO for LDLT using a right hemiliver graft with a graft‐to‐recipient body weight ratio > 0.9% and <30% steatosis can be a tolerable procedure for donors and recipients. Liver Transpl 18:130–138, 2012. © 2011 AASLD.