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Abstract We aim to develop a nomogram to predict overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosystemic shunt (TIPS) in patients with portal hypertension, according to demographic/clinical indicators such as age, creatinine, blood ammonia, indocyanine green retention rate at 15 min (ICG-R15) and percentage of Portal pressure gradient (PPG) decline. In this retrospective study, 296 patients with portal hypertension who received elective TIPS in Beijing Shijitan Hospital from June 2018 to June 2020 were included. These patients were randomly divided into a training cohort (n = 207) and a validation cohort (n = 89). According to the occurrence of OHE, patients were assigned to OHE group and non-OHE group. Both univariate and multivariate analyses were performed to determine independent variables for predicting OHE after TIPS. Accordingly, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to compare the accuracy and superiority of a novel model with conventional Child–Pugh and MELD scoring model. Age (OR 1.036, 95% CI 1.002–1.070, p = 0.037), Creatinine (OR 1.011, 95% CI 1.003–1.019, p = 0.009), Blood ammonia (OR 1.025, 95% CI 1.006–1.044, p = 0.011), ICG-R15 (OR 1.030, 95% CI 1.009–1.052, p = 0.004) and Percentage decline in PPG (OR 1.068, 95% CI 1.029–1.109, p = 0.001) were independent risk factors for OHE after TIPS using multifactorial analysis. A nomogram was constructed using a well-fit calibration curve for each of these five covariates. When compared to Child–Pugh and MELD score, this new nomogram has a better predictive value (C-index = 0.828, 95% CI 0.761–0.896). Consistently, this finding was reproduceable in validation cohort and confirmed with DCA. A unique nomogram was developed to predict OHE after TIPS in patients with PHT, with a high prediction sensitivity and specificity performance than commonly applied scoring systems.