Control of bleeding remains key to successful hepatic resection. The present randomized clinical trial compared infrahepatic inferior vena cava (IVC) clamping with low central venous pressure (CVP) during complex hepatectomy using portal triad clamping (PTC). Methods: Consecutive patients undergoing complex hepatectomy were allocated randomly to PTC combined with infrahepatic IVC clamping or to PTC with low CVP. Primary outcome was blood loss during parenchymal transection. Secondary outcomes were intraoperative surgical and haemodynamic parameters, postoperative recovery of liver and renal function, postoperative morbidity and mortality, and duration of hospital stay. Results: Between January 2008 and September 2010, 192 patients were randomized. Compared with low CVP, infrahepatic IVC clamping significantly decreased blood loss during parenchymal transection (mean(s.e.m.) 243(158) versus 372(197) ml; P < 0.001), was associated with faster recovery of liver function, and caused less impairment in renal function and fewer haemodynamic changes. The degree of cirrhosis correlated positively with CVP (R2 = 0.963, P = 0.019) and with infrahepatic IVC pressure (R2 = 0.950, P = 0.025). For patients with moderate or severe cirrhosis, infrahepatic IVC clamping was more efficacious in controlling blood loss during parenchymal transection (mean(s.e.m.) 2.9(1.8) versus 6.1(2.4) ml/cm2; P < 0.001). Conclusion: PTC combined with infrahepatic IVC clamping is more efficacious in controlling bleeding during complex hepatectomy than PTC with low CVP, especially in patients with moderate to severe cirrhosis. Registration number: NCT01355887 . Copyright (C) 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.