The Strategic Plan for Tackling Hepatitis C launched in 2015 in Spain has led to an important nationwide decrease in hepatitis C related hospitalisation rates. However, patients' infection progression during decades could increase their health status complexity and challenge patient's prognosis after hepatitis C eradication.We carried out an observational retrospective study evaluating the prevalence of the main co-infections, comorbidities (risk factors and extrahepatic manifestations), and alcohol or other substances abuses in chronic hepatitis C related hospitalised patients in Spain. Data were obtained from the National Hospitalisation Registry discharges from January 1st of 2012 to December 31st of 2019.Between 2012 and 2019 there were 356,197 chronic hepatitis C-related hospitalisations. In-hospital deaths occurred in 11,558 (4.6%) non-advanced liver disease and in 10,873 (10.4%) advanced liver disease-related hospitalisations. Compared to 2012-2015, in 2016-2019 the proportion of hospitalisations related to non-advanced liver disease increased from 69.4% to 72.4%, while the advanced disease-related hospitalisations decreased from 30.6% to 27.6% (P.001). In spite of the decrease in severe cases among hospitalisations, all comorbidities evaluated, and alcohol abuse increased in 2016-2019 compared to 2012-2015, while co-infections and other substances abuses decreased in the same period. In the latest period (2016-2019): 28,679 (18.3%) of the hospitalised patients had a HIV, 6928 (4.4%) a hepatitis B, and 972 (.6%) a tuberculosis co-infection. Most frequent comorbidities were diabetes (N=33,622; 21.5%); moderate to severe renal disease (N=28,042; 17.9%), chronic obstructive pulmonary disease and asthma (N=25,559; 16.3%), and malignant neoplasms (excluding hepatocellular carcinoma) (N=19,873; 12.7%). Alcohol or substances abuse was reported in 48,506 (31.0%) hospitalisations: 30,782 (19.7%) with alcohol; 29,388 (18.8%) with other substances; and 11,664 (7.5%) with both, alcohol and other substances, abuses.Despite the reduction in advanced liver disease hepatitis C-related hospitalisations due to prioritisation of treatment to the more severe cases, high and increasing prevalence of comorbidities and risks factors among hepatitis C-related hospitalisations have been found.