Abstract Background The intermittent Pringle manoeuvre (IPM) is commonly applied during liver resection. Few randomized trials have addressed its effectiveness in reducing blood loss and the results have been conflicting. The present study investigated the hypothesis that IPM could reduce blood loss during liver resection by 50 per cent. Methods Between May 2008 and April 2011, patients who underwent elective open hepatectomy were randomized into an IPM or no Pringle manoeuvre (NPM) group and stratified according to the presence or absence of cirrhosis. Data on demographics, type of hepatectomy, operative blood loss, duration of operation, mortality, morbidity and postoperative liver function were recorded and analysed. The primary endpoint was operative blood loss. Results There were 63 patients in each group. Median (range) operative blood loss was 370 (50–3600) ml in the IPM group versus 335 (40–3160) ml in the NPM group (P = 1·000). There were no differences in blood loss in different phases of the operation, blood loss per area of liver transected or blood transfusion rate, nor in total duration of operation or liver transection time. Postoperative serum alanine aminotransferase levels were higher in the IPM group (P < 0·001). There were more postoperative complications in the IPM group (41 versus 24 per cent; P = 0·036). Conclusion The IPM did not reduce blood loss, but was associated with raised levels of postoperative liver parenchymal enzymes and more complications. Registration number: NCT00730743 (http://www.clinicaltrials.gov).