Today, mechanical ventilation devices play an effective role in the improvement of patients. Prolonged mechanical ventilation and inappropriate weaning of patients from ventilators have undesirable consequences. To measure the readiness of patients to be weaned from a ventilator, accurate and valid criteria are required. The present study was conducted to compare SOFA with APACHEII scores in predicting the results of weaning patients from the ventilator in the intensive care unit (ICU). This was a descriptive-analytic study of comparative type conducted in 2015 in Isfahan, Iran on patients admitted to the ICU. The study sample was all patients admitted to the ICU of Amin Hospital. Sampling was conducted using the convenience (accessible) sampling method. Overall, 85 patients comprised our sample. Of the 85 patients, 24 patients died and were excluded from the study. In this study, the standard forms of SOFA and APACHEII were used to score patients' conditions. Descriptive statistical tests and the t-test, logistic regression, correlation coefficient, and calculation of specificity, sensitivity and area under ROC curve were used. Then, the data were analyzed using SPSS18 software. In this study, of the 61 patients included in the sample, 15 patients (24.6%) were females and 46 patients (75.4%) were males. In terms of age, the highest frequency distribution was related to patients over 70 years (18%), and 60.7% of the patients had an underlying disease. This study showed that there is a significant relationship between the SOFA and APACHEII scores. However, the values of sensitivity, specificity, positive predictive value, negative predictive value, and area under the ROC curve were higher in the APACHEII scoring system than in SOFA. In addition, the APACHEII score at admission and at first weaning predicted the result of the first weaning of patients from the ventilator. On the other hand, the mortality rate was zero percent in patients who first their weaning of ventilator was successful. While there is a significant relationship between the SOFA and APACHEII scores, the APACHEII scores were a better indicator than SOFA for predicting successful weaning of the patient from ventilator. Also this study show that failure at the first weaning of the patients from ventilator accompanies an increase of mortality.