A bstract Aims and objectives Different severity scores are being used to assess outcomes in intensive care unit, but variable data had been reported so far per their performance. Main objective of this study is to compare performance of acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), and modified nutrition risk in critically ill (mNUTRIC) scoring systems regarding the outcomes in the form of morbidity and mortality in medical intensive care unit (MICU) at rural tertiary-care health center. Materials and methods In this cross-sectional study, 1,990 patients older than 18 years admitted in the ICU were enrolled. Age, gender, diagnosis, intubation, comorbidities, APACHE II, SOFA scores, m NUTRIC score, MICU stays in days, and need of mechanical ventilation were noted. Results When we compared different score with mortality, APACHE-II was having sensitivity of 89.9% and specificity of 97.6%; SOFA had 90.1% sensitivity and 96.6% specificity; while mNUTRIC score had 97.2% sensitivity and 74.0% specificity. APACHE-II score had sensitivity of 93.4%, SOFA had 90.5%, and mNUTRIC score 92.3% with low specificity of 76.5% in predicting requirement of mechanical ventilation. mNUTRIC score and ICU length of stay showed moderate positive correlation ( p value = <0.001). Conclusion All the three scores were comparable in sensitivity and specificity in predicting outcomes in the form of mortality, need of mechanical ventilation, and length of ICU stays. mNUTRIC score was more sensitive than others, and as it was based on nutritional status, hence more weightage should be given on this score. How to cite this article Kumar S, Gattani SC, Baheti AH, Dubey A. Comparison of the Performance of APACHE II, SOFA, and mNUTRIC Scoring Systems in Critically Ill Patients: A 2-year Cross-sectional Study. Indian J Crit Care Med 2020;24(11):1057–1061.