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BaCKgRoUND aND aIMS:Infection is a major driver of mortality in patients with advanced alcohol-associated liver disease (ALD). The epidemiology and clinical course of patients infected with life-threatening forms of ALD, including severe alcohol-associated hepatitis (sAH) and decompensated alcohol-associated cirrhosis (DAC), and specific risk factors for infection remain mostly unknown. appRoaCH aND ReSUltS:In this observational study, we assessed all infectious episodes occurring within a 90-day period from diagnosis in all consecutive patients with biopsyproven sAH (modified Maddrey's discriminant function ≥ 32, Model for End-Stage Liver Disease [MELD] ≥ 18) and DAC (MELD ≥ 18) without alcohol-associated hepatitis in our tertiary hospital between 2003 and 2016. A total of 207 patients were included: 139 with sAH and 68 with DAC. One hundred seventeen (84%) patients with sAH and 41 (60%) patients with DAC experienced at least one infection episode at 90 days (P < 0.001). In multivariable analysis, factors associated with the development of infection were the presence of sAH and baseline MELD score. Bacterial infections represented the most common infection in the two groups, and only the MELD score was independently associated with the occurrence of bacterial infection. In both groups, pneumonia was the most prevalent bacterial infection, and gram-negative bacilli were the main pathogens. Invasive fungal infections (IFI) occurred in 20 (14.5%) patients with sAH and 3 (4.5%) with patients with DAC (P < 0.05). Multivariable regression showed that younger age, higher MELD, and corticosteroid therapy were independently associated with IFI. The 90-day cumulative incidence of death in patients infected with sAH and patients infected with DAC was 46% and 41.5%, respectively (P = 0.43). CoNClUSIoNS:Patients with sAH are more susceptible to develop infection than those with DAC. In life-threatening forms of ALD, patients who were infected share a similar mortality rate. Corticosteroid treatment, not sAH, seems to be the main risk factor triggering IFI. (Hepatology 2021;74:2714-2724.A lcohol-associated liver disease (ALD) is one of the most prevalent causes of advanced liver disease around the world. (1) The most severe forms of ALD include decompensated alcoholassociated cirrhosis (DAC) and severe alcoholassociated hepatitis (sAH), which is frequently superimposed on cirrhosis. Infections, mainly bacterial, are frequent in these patients, and severe complications of infection can occur with advanced ALD. In the first 28 days after the diagnosis of sAH, the incidence of infection is estimated to be between 20% and 50%. (2)(3)(4) Infection also strongly predicts the development of acute-on-chronic liver failure (ACLF).