Background & Aims: Different scoring systems are used in order to assess the functional quality of intensive care units (ICU) and to predict the required costs and facilities of intensive cares. Variety of scoring systems has been explained that each has advantages and disadvantages. In this study Simplified Acute Physiology Score-III (SAPS-III) and Mortality Probability MODEL-III (MPM-III) were compared. Materials & Methods: The current cross-sectional study was conducted on 240 non-traumatic patients admitted at ICU of Al-Zahra Hospital in 2016-17. Patients' information including demographics, mean of systolic, diastolic and arterial pressure, pulse rate, respiratory rate, temperature, Glasgow Coma Scale(GCS), WBC, hematocrit, bilirubin, creatinine, arterial blood gas, and the presence of underlying diseases was gathered from the records for measurement of MPM-III and SAPS-III scores and then they were compared. Results: This study was conducted on 240 non-traumatic patients. Discrimination of MPM-III in cutoff point of 0. 17 was 0. 83(P<0. 001; 95%CI: 0. 765-0. 898), sensitivity and specificity of this test in prediction of non-traumatic mortality was 82% and 73%, respectively. Discrimination of SAPS-III in cut-off of 48. 5 was 0. 78(P<0. 001; 95%CI: 0. 72-0. 84), while its sensitivity and specificity was 83% and 70%, respectively. Duration of ICU hospitalization (P=0. 028 and 0. 002) and duration of intubation (P=0. 001 and <0. 001) had direct association with mortality based on both scoring systems while total duration of hospitalization was only significant in SAPSIII (P=0. 002). Conclusion: Comparison of SAPS-III and MPM-III in non-traumatic patients presented a higher discrimination ability for MPM-III. In addition, findings showed that mortality in MPM-III was in association with duration of ICU admission and intubation while for SAPS-III, in addition to previous factors, total duration of hospitalization was associated as well.