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Abstract : Background and Aim: Plasma exchange (PLEX) has recently been shown to improve survival in acute liver failure (ALF); however, there is no study specifically analyzing its utility in Hepatitis A virus related ALF (HAV-ALF). ALF patients who are not on inotropes tolerate PLEX better (PMID: 39001974). We aimed to compare efficacy of PLEX and of standard medical treatment (SMT) to treat HAV-ALF. Methods: We retrospectively compared consecutive HAV-ALF patients treated with PLEX between 2018-2024 with SMT between 2011-2024 in 12 centres across India. We compared in-hospital liver transplant (LT)-free survival between PLEX and SMT groups in whole cohort. In the subset of patients not on inotropes; we compared survival in PLEX and SMT groups; and assessed predictors of survival. Poor outcome was defined as death or discharge in moribund state. Results: Eighty-four HAV-ALF patients in PLEX group (61 males; age: 23.5, 21-33 years, median, IQR; Kings college criteria fulfilled (KCC): 22, 26.2%) and 150 HAV-ALF in SMT group (101 males; age: 24, 19-32.3 years; KCC fulfilled: 16, 10.7%) were studied. No patient underwent LT. Overall, in-hospital survival was comparable in PLEX (70.2%) and the SMT group (65.3%; p-value: 0.47). On subgroup analysis of patients not on inotropes, in-hospital survival in PLEX group (52/54; 96.3%) was significantly better than in SMT group (81/104; 77.9%) (p value: 0.002). In patients not on inotropes, predictors of poor outcome were HE grade 3, need for mechanical ventilation, high SOFA, MELD, ALFA scores or those who fulfilled >2 poor prognostic ALFSG criteria (p value <0.001). Conclusion: PLEX improves in-hospital liver transplant-free survival in HAV-ALF patients not on inotropes compared to SMT. This points to an optimal window to select HAV-ALF patients for PLEX treatment.