Objective To examine the adrenal function of critically ill patients received mechanical ventilation, and explore the relationship between the occurrence of relative adrenal insufficiency ( RAI) and weaning outcome.Methods Critically ill patients who were mechanically ventilated over 48 hours were enrolled in this study. Every patient was given one shot of corticotrophin 250 μg intravenously on the first day of admission and the first day of spontaneous-breathing-trial ( SBT) . Plasma contisol level was detected by radio-immunoassay before ( T0 ) and 30 minutes ( T30 ) after the shot. Meanwhile the following parameters were recorded including APACHEⅡ, age, and cause of disease, etc. RAI was defined as the difference between T0 and T30 ≤9 μg/dL. Receiver operating characteristic ( ROC) curve was used to evaluate the accuracy of the indicators towards the weaning outcome. Results A total of 45 patients with mechanical ventilation were recruited. The successful weaning group consisted 29 patients and the failure weaning group consisted 16 patients. The incidence of RAI in the successful weaning group ( 37.9% , 11/ 29) was significantly lower than that in the failure weaning group ( 75.0% , 12 /16) ( P=0. 017) . On the first day of admission, there was no significant difference of Δcortisol between the successful weaning group and the failure weaning group [ ( 10.3 ±5.7) μg/dL vs. ( 7.5 ±4.5) μg/dL, P=0.100) . On the first SBT day, Δcortisol of the successful weaning group was significantly higher than that in the failure weaning group [ ( 10.9 ±5.1) μg/dL vs. ( 4.9 ±2.9) μg/dL, P= 0.043] . Logistic regression analysis showed that Δcortisol was an independent risk factor of weaning. ROC curve analysis showed that on the first SBT day, the area under the curve of Δcortisol was 0.872; The sensitivity and the specificity of accurate judgmentwere 0.813 and 0.828 if Δcortisol ≤6. 95 μg/dL. Conclusions The occurrence of RAI is common in critically ill patients with mechanical ventilation. The adrenal function affects the outcome of weaning, and Δcortisol may be used as an important predictive indicator for weaning outcome.