Introduction: Paracetamol is often used as an analgesic following hepatic resection. During liver resection, vascular clamping is carried out to reduce blood loss. Previous studies have described transient postoperative rises in serum aminotransferase levels and decreases in prothrombin time and factor V levels. We have examined paracetamol metabolism after liver resection. Methods: A prospective observational study was performed. All patients undergoing liver resection were included. Propacetamol was given every 6 h. Blood samples for plasma paracetamol concentrations were collected before, 1 h after the end of the first injection (T1), just before the second injection (6 h: T6), and just before the fifth injection (24 h: T24). Results: 37 patients were recruited. 13 had hepatic vascular exclusion (HVE group), 13 had portal triad clamping (PTC group) and 11 had abdominal surgery with no liver resection (NLR group: control group). At T6, the plasma paracetamol concentration in the HVE group was significantly higher than in the NLR groups; at T24, this concentration was significantly higher in the HVE group than in the NLR and PTC groups, and was higher in the PTC group than in the NLR group. Prothrombin time and factor V was significantly lower in the HVE group than in the PTC group on the first postoperative day. Discussion: This study showed a reduction of paracetamol metabolism in the liver resection group with significantly increased paracetamol levels. However, the maximum mean plasma concentration reached was not clinically or toxicologically significant. For these reasons, we cannot suggest that paracetamol should or should not be avoided in patients undergoing liver resection.