Background: Gas embolism is a potential hazard during laparoscopic procedures. The aim of this study was to evaluate the effects of nitrous oxide (N2O) inhalation in the case of gas embolism with carbon dioxide (CO2) and helium during pneumoperitoneum. Methods: For this study, 20 anesthetized pigs were ventilated with N2O (67% inspired) in O2 (n= 10) or with halothane (0.7–1.5 inspired) in O2 (n= 10). In each group, CO2 (n= 5) or helium (n= 5) pneumoperitoneum was established and gas embolism induced at different rates (CO2 at 0.5, 1, or 2 ml/kg/min; helium at 0.025, 0.05, or 0.1 ml/kg/min) through the left femoral vein a maximum of 10 min while all hemodynamic parameters were continuously monitored. Results: In the CO2 group without N2O, all the animals tolerated rates of 0.5 and 1 ml/kg/min over the 10 min, whereas only 3 of 4 animals in the CO2 group with N2O tolerated a rate of 0.5 ml/kg/min, and 2 of 4 animals a rate of 1 ml/kg/min. In the helium group without N2O, all the animals tolerated gas embolism at all rates, whereas in the helium group with N2O, 4 of 5 animals needed to be resuscitated at a rate of 0.1 ml/kg/min and one death occurred. Conclusions: Inhalation of N2O worsens the negative cardiovascular effects of venous CO2 or helium gas emboli and increases the risk of emboli-induced death when CO2 or helium are used to establish pneumoperitoneum. The volume of venous venous helium gas emboli causing such effects is substantially smaller than that for venous CO2 gas emboli.