Background. This study evaluated whether large venous-arterial CO2 gap (PCO2 gap) preoperatively is associated to poor outcome. Method. Prospective study which included adult high-risk surgical patients. The patients were pooled into two groups: wide [P(v-a)CO2] versus narrow [P(v-a)CO2]. In order to determine the best value to discriminate hospital mortality, it was applied a ROC (receiver operating characteristic) curve for the [P(v-a)CO2] values collected preoperatively, and the most accurate value was chosen as cut-off to define the groups. Results. The study included 66 patients. The [P(v-a)CO2] value preoperatively that best discriminated hospital mortality was 5.0 mmHg, area = 0.73. Preoperative patients with [P(v-a)CO2] more than 5.0 mmHg presented a higher hospital mortality (36.4% versus 4.5% P = 0.004), higher prevalence of circulatory shock (56.8% versus 22.7% P = 0.01) and acute renal failure postoperatively (27.3% versus 4.5% P = 0.02), and longer hospital length of stays 20.0 (14.0–30.0) versus 13.5 (9.0–25.0) days P = 0.01. Conclusions. The PCO2 gap values more than 5.0 mmHg preoperatively were associated with worse postoperatively outcome.