INTRODUCTION: Cholecystectomy is the intervention of choice for treating acute cholecystitis; when conservative management does not work, it operates on the patient outside the critical condition. It can be performed together with or after endoscopic papillotomy through endoscopic retrograde cholangiopancreatography (ERCP) when it is concurrent with a situation of cholechodocolithiasis or when there is compression and consequent increase in pressure in the bile duct caused by a calculus jammed in the vesicular infundibulum (Mirizzi's syndrome), with or without jaundice, fever, and pain in the right hypochondrium (Charcot's Triad), which can progress to sepsis of biliary origin. This review aims to assess whether the timing of cholecystectomy (before or after ERCP) interferes with the postoperative period and clinical outcome in patients with acute cholecystitis. METHODS AND ANALYSIS: By searching the MEDLINE/PubMed, Embase, Web of Science, ScienceDirect, ClinicalTrials.gov, CINAHAL, Latin American and Caribbean Literature in Health Sciences, Scopus and Cochrane Central databases, Controlled Trials Registry Randomized clinical trials will be searched to analyze whether ERCP performed before or after open or laparoscopic cholecystectomy (LC) in patients with acute cholecystitis is beneficial or not, through the analysis of postoperative complications. No language or publication period restrictions will be imposed. The primary outcome will be postoperative complications (postoperative morbidity and mortality). Four independent reviewers will select the studies and extract data from the original publications, with a fifth reviewer in case of disagreement regarding the inclusion or not of particular research in the present review. The risk of bias will be assessed using The Risk of Bias 2 (RoB 2.0) tool, and the certainty of evidence will be evaluated using the grading of recommendations assessment, development, and evaluation. Data synthesis will be performed using the Review Manager software (RevMan V.5.2.3). To assess heterogeneity, we will calculate the I2 statistics. Additionally, a quantitative synthesis will be performed if the included studies are sufficiently homogeneous. ETHICS AND DISCLOSURE: Since the present study will review secondary data, previously published and scientifically validated, it will not be necessary to obtain ethical approval. The results of this systematic review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: International Prospective Registry of Systematic Reviews (PROSPERO) CRD42021290726.