Introduction. The aim of this study was to assess the interaction of liver and renal dysfunction as risk factors for mortality after liver resection. Materials and Methods. A retrospective analysis of 501 patients undergoing liver resection in a single unit was undertaken. Posthepatectomy liver failure (PHLF) was defined according to the International Study Group of Liver Surgery (ISGLS) definition (assessed on day 5) and renal dysfunction according to RIFLE criteria. 90-day mortality was recorded. Results. Twenty-three patients died within 90 days of surgery (4.6%). The lowest mortality occurred in patients without evidence of PHLF or renal dysfunction (2.7%). The mortality rate in patients with isolated PHLF or renal dysfunction was 20% compared to 45% in patients with both. Diabetes (P = 0.028), renal dysfunction (P = 0.030), and PHLF on day 5 (P = 0.011) were independent predictors of 90-day mortality. Discussion. PHLF and postoperative renal dysfunction are independent predictors of 90-day mortality following liver resection but the predictive value for mortality is significantly higher when failure of both organ systems occurs simultaneously.