BACKGROUND Arterial blood gas (ABG) analysis is useful in evaluation of the clinical condition of critically ill patients; however, arterial puncture or insertion of an arterial catheter may cause many complications. The aim of this study was to determine whether venous blood gas (VBG) values can be used as an alternative to arterial blood gas measurements in patients under mechanical ventilation. METHODS This study was carried out on patients admitted to the Intensive Care Unit of Kashan Beheshti Hospital. Blood for VBG analysis was obtained from the cubital vein, while for ABG analysis blood was taken simultaneously from the radial artery. ABG and VBG samples were obtained simultaneously, and indexes of pH, PCO2, HCO3, base excess (BE), PO2 and O2 saturation level were analyzed. RESULTS A total of 102 pair of simultaneous venous and arterial blood samples were obtained from 102 patients (mean age 58.4±21.5 years). Seventy (69%) were males. The mean difference between arterial and venous values was 0.04 for pH, 5.6 mm/Hg for PCO2, -0.32 mmol/l for HCO3, -1.03 mmol/l for BE, 53.6 mm/Hg for PO2, and 23.5% for O2 saturation. The Pearson correlation coefficients between arterial and venous values for pH, PCO2, HCO3, BE, PO2 and O2 saturation were 0.874, 0.835, 0.768, 0.810, 0.287, and 0.310, respectively. Linear regression equations for the estimation of pH, PCO2, HCO3, BE, PO2 and O2 saturation were as follows: arterial pH=1.927+0.745×venous pH [r=0.801, p<0.001]; PCO2=6.470+0.706×venous PCO2 [r=0.835, p<0.001]; arterial HCO3=7.455+0.681×venous HCO3 [r=0.768, p<0.001]; arterial BE=-0.952+0.736×venous BE [r=0.810, p<0.001]; arterial PO2=70.374+0.620×venous PO2 [r=0.287, p=0.003]; arterial venous saturation= 89.753+0.082×venous O2 saturation [r=0.317, p=0.001]. CONCLUSIONS Venous blood gases, especially pH, Base excess, and PCO2 levels have relatively good correlation with ABG values. Because this correlation is not close, VBG cannot substitute ABG in mechanically ventilated patients.