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Background & Aims: Severe acute liver injury (ALI) precedes acute liver failure (ALF). Risk factors related to ALI progression to ALF or death, are not well-known. We aimed to investigate which predictors of poor outcomes can be identified in patients with ALI. Methods: We retrospectively analyzed 59 patients with ALI diagnosis, admitted from 2010 to 2021 in our Intermediate Medical Care Unit, and checked for clinical, biochemical and imagiological data, in order to explore their relationship with progression to ALF or death. Results: From the 59 patients with ALI, 11 (18.6%) evolved to ALF and 9 (15.3%) died during the hospital staying or within the first month after discharge. Not having drug-induced liver injury or ischemic hepatitis as etiological factors was associated to increased progression to ALF (hazard ratio [HR] 0.17; 95% confidence interval [CI]: 0.03-0.96; P=0.041). In univariate analysis, ascites related to development to ALF (HR 0.25; 95% CI: 0.06-0.97; P=0.037) and death (HR 7.09; 95% CI: 1.55-33.04; P=0.006), while renal dysfunction, was only allied to death (HR 0.99; 95% CI: 0.97-1.00; P=0.035). Inflammatory markers at admission were not linked to progression to ALF. Yet, increased C reactive-protein levels were commonly found in patients who died (HR 1.01; 95% CI: 1.00-1.03; P=0.035). In multivariate analysis, only ascites remained significant (P=0.005) as predictor of death. Conclusions: In patients with ALI, ascites at presentation is the only marker of poor prognosis (mainly to death). Still, those who are more inflamed or have renal dysfunction at baseline are more willing to die.