This study affords a prediction tool, the Early Prediction of Decompensation (EPOD) score, for the risk of decompensation in patients with cirrhosis. This score demonstrated better performance than well-known cirrhosis scores. Because EPOD is based on three blood parameters, only, it offers maximal clinical feasibility at minimal costs.

• This study included 6,049 cirrhosis patients in the IBM Explorys database training cohort as well as the IBM Explorys database validation cohort (N = 17,662), the Penn Medicine BioBank (N = 1,326) and the UK Biobank (N = 317).

• The new EPOD score uses platelet count, albumin, and bilirubin level.

• This score enabled decompensation prediction during a 3-year follow-up in three validation cohorts with areas under the receiver operating characteristic of 0.69, 0.69 and 0.77, respectively, and displayed superior performance than the well-known MELD and Child-Pugh score in predicting decompensation.

• Furthermore, prediction of the 3-year likelihood of decompensation was achieved with the EPOD score.