Background: Acute hypotensive episodes (AHE), defined as a drop in the mean arterial pressure (MAP) <65 mm Hg lasting at least 5 consecutive minutes, are among the most critical events in the intensive care unit (ICU). They are known to be associated with adverse outcome in critically ill patients. AHE prediction is of prime interest because it could allow for treatment adjustment to predict or shorten AHE. Methods: The Super Learner (SL) algorithm is an ensemble machine-learning algorithm that we specifically trained to predict an AHE 10 minutes in advance. Potential predictors included age, sex, type of care unit, severity scores, and time-evolving characteristics such as mechanical ventilation, vasopressors, or sedation medication as well as features extracted from physiological signals: heart rate, pulse oximetry, and arterial blood pressure. The algorithm was trained on the Medical Information Mart for Intensive Care dataset (MIMIC II) database. Internal validation was based on the area under the receiver operating characteristic curve (AUROC) and the Brier score (BS). External validation was performed using an external dataset from Lariboisière hospital, Paris, France. Results: Among 1151 patients included, 826 (72%) patients had at least 1 AHE during their ICU stay. Using 1 single random period per patient, the SL algorithm with Haar wavelets transform preprocessing was associated with an AUROC of 0.929 (95% confidence interval [CI], 0.899-0.958) and a BS of 0.08. Using all available periods for each patient, SL with Haar wavelets transform preprocessing was associated with an AUROC of 0.890 (95% CI, 0.886-0.895) and a BS of 0.11. In the external validation cohort, the AUROC reached 0.884 (95% CI, 0.775-0.993) with 1 random period per patient and 0.889 (0.768-1) with all available periods and BSs <0.1. Conclusions: The SL algorithm exhibits good performance for the prediction of an AHE 10 minutes ahead of time. It allows an efficient, robust, and rapid evaluation of the risk of hypotension that opens the way to routine use.