Serum sodium (Na) has been suggested for incorporation into the Model for End-Stage Liver Disease (MELD) to enhance its prognostic ability for patients with cirrhosis. Three Na-containing models--the Model for End-Stage Liver Disease with the incorporation of serum sodium (MELD-Na), the integrated Model for End-Stage Liver Disease (iMELD), and the Model for End-Stage Liver Disease to sodium (MESO) index--were independently proposed for this purpose. This study investigated the accuracy of these 4 MELD-based models for outcome prediction. The c-statistic equivalent to the area under the receiver operating characteristic curve (AUC), used to predict 3- and 6-month mortality, was calculated and compared in 825 patients with cirrhosis. The MELD score tended to be lower with increasing Na level. At 3 months of enrollment, the iMELD had the highest AUC (0.807) and was followed by the MELD-Na (0.801), MESO (0.784), and MELD (0.773); the difference between the MESO and MELD was statistically significant (P = 0.013). At 6 months, the iMELD still had the highest AUC (0.797) and was followed by the MELD-Na (0.778), MESO (0.747), and MELD (0.735); all comparisons showed significant differences between each other (all P < 0.01), with the exception of iMELD and MELD-Na (P = 0.18). With the most discriminative cutoffs, the specificity and negative predictive value were 70%-85% and 89%-97%, respectively, at 3 and 6 months for the 4 models. Patients with spontaneous bacterial peritonitis (SBP) consistently had significantly higher MELD-derived scores in all 4 models compared to patients without SBP (all P < 0.01). Patients with hepatic encephalopathy also had higher scores in all 4 models, although the statistical significance was established only for the iMELD (41.0 +/- 11.5 versus 37.6 +/- 9.1, P = 0.037). In conclusion, the incorporation of Na into the MELD may enhance prognostic accuracy. Both the iMELD and MELD-Na are better prognostic models for outcome prediction in patients with cirrhosis. Patients with SBP have a higher MELD-derived score. Future studies are warranted to define the optimal MELD-based prognostic model for cirrhosis.