Complications of liver cirrhosis (LC) are the main cause of hospital admissions in liver units. In areas where hepatitis C virus (HCV) is highly prevalent, most of these admissions are attributable to HCV-LC. We aimed to assess the impact of direct-acting antivirals (DAA) in the profile of liver disease patients admitted into a referral liver unit from a University Hospital.We registered hospital admissions due to LC in our Liver Unit from 2011-2014 (pre-DAA period) and from 2015-2019 (post-DAA period).From a total of 14,865 hospital admissions, 10,053 were due to LC (corresponding to 6,256 patients). The number and proportion of hospital admissions due to HCV-LC remained stable during the period 2011-2014 (525 per year, 48.8% of the total), but decreased progressively after 2015 (p<0.001), reaching less than 300 (27.1%) admissions in 2019. Similarly, HCV-LC accounted for 3,885 inpatient days per year (44.9%) during the pre-DAA period and decreased steadily after 2015 (p >0.001), reaching only 1,909 inpatient days (22%) in 2019. The figures for intensive care unit admissions followed a similar pattern. By means of a slope analysis (binomial regression model) we predicted that HCV-LC hospital admissions will be residual by 2025 (2.3%, 95% CI 0-10.9%). On the other hand, we observed a significant increase in hospital admissions due to metabolic associated fatty liver disease (5-fold) and autoimmune hepatitis (4-fold) during the study period.In summary, our data show a profound reduction in HCV-LC hospitalization burden since 2015, coincident with the wide use of DAA in Spain. Our predictions suggest that in 2025, HCV-LC will be a marginal cause of hospital admissions for liver disease patients.