BACKGROUND The optimal timing of endoscopic retrograde cholangiopancreatography (ERCP) in acute cholangitis (AC) is uncertain, especially in patients with AC of varying severity. AIM To report whether the timing of ERCP is associated with outcomes in AC patients with different severities. METHODS According to the 2018 Tokyo guidelines, 683 patients who met the definite diagnostic criteria for AC were retrospectively identified. The results were first compared between patients receiving ERCP ≤ 24 h and > 24 h and then between patients receiving ERCP ≤ 48 h and > 48 h. Subgroup analyses were performed in patients with grade I, II or III AC. The primary outcome was 30-d mortality. Secondary outcomes were intensive care unit (ICU) admission rate, length of hospital stay (LOHS) and 30-d readmission rate. RESULTS Taking 24 h as the critical value, compared with ERCP > 24 h, malignant biliary obstruction as a cause of AC was significantly less common in the ERCP ≤ 24 h group (5.2% vs 11.5%). The proportion of cardiovascular dysfunction (11.2% vs 2.6%), respiratory dysfunction (14.2% vs 5.3%), and ICU admission (11.2% vs 4%) in the ERCP ≤ 24 h group was significantly higher, while the LOHS was significantly shorter (median, 6 d vs 7 d). Stratified by the severity of AC, higher ICU admission was only observed in grade III AC and shorter LOHS was only observed in grade I and II AC. There were no significant differences in 30-d mortality between groups, either in the overall population or in patients with grade I, II or III AC. With 48 h as the critical value, compared with ERCP > 48 h, the proportion of choledocholithiasis as the cause of AC was significantly higher in the ERCP ≤ 48 h group (81.5% vs 68.3%). The ERCP ≤ 48 h group had significantly lower 30-d mortality (0 vs 1.9%) and shorter LOHS (6 d vs 8 d). Stratified by AC severity, lower 30-d mortality (0 vs 6.1%) and higher ICU admission rates (22.2% vs 10.2%) were only observed in grade III AC, and shorter LOHS was only observed in grade I and II AC. In the multivariate analysis, cardiovascular dysfunction and time to ERCP were two independent factors associated with 30-d mortality. CONCLUSION ERCP ≤ 48 h conferred a survival benefit in patients with grade III AC. Early ERCP shortened the LOHS in patients with grade I and II AC.