Since weaning failure is multifactorial, comprehensive weaning scores encompassing not only the respiratory component but also nonrespiratory aspects are quintessential for successful weaning prediction. This was a single-center prospective observational study on 128 intensive care unit (ICU) patients undergoing spontaneous breathing trials (SBT). The extubation prediction score (ExPreS), heart rate, acidosis, consciousness, oxygenation, respiratory rate (HACOR), and weaning parameters, endotracheal tube size, arterial blood gas analysis, nutrition, secretions, neuromuscular affecting agents, obstructive airway problems and wakefulness (WEANSNOW) scores were compared for their diagnostic accuracy for successful weaning prediction. Out of 128 patients, 49 (38.3%) patients had weaning failure, and 79 (61.7%) had weaning success. The patients in the weaning failure group had significantly higher APACHE II scores, WEANSNOW scores, HACOR scores, MV days, and significantly lower ExPreS scores as compared to the successful weaning group. Multivariable regression analysis showed that ExPreS score p = 0.015, adjusted OR 0.960, 95% CI (0.929-0.992) and HACOR score p < 0.001, adjusted OR 1.357, 95% CI (1.176-1.567) were independent predictors of weaning failure. The HACOR score had an AUC of 0.830, cut-off ≥5, p < 0.001, sensitivity 76%, specificity 68%, diagnostic accuracy 70% to predict weaning failure. The ExPreS score had an AUC of 0.735, cut-off ≥69, p < 0.001, sensitivity of 70.9%, specificity of 69.4%, and diagnostic accuracy of 70.3% to predict weaning success. Both the HACOR and ExPreS scores were good models for predicting weaning outcomes (model quality 0.76 and 0.64 respectively). The parsimonious HACOR score is comparable to the ExPreS score for the prediction of weaning outcomes in critically ill patients. Nayak G, Chaudhuri S, Ravindranath S, Todur P. Comparison of the Recent ExPreS Score, WEANSNOW Score, and the Parsimonious HACOR Score as the Best Predictor of Weaning: An Externally Validated Prospective Observational Study. Indian J Crit Care Med 2024;28(3):273-279.