Alcohol dependence (AD) is associated with an increase of physical comorbidity but the effects of these diseases on hospital-based mortality are unclear. Objectives and aims. To investigate whether the burden of physical comorbidity and its relevance on general hospital-based mortality differs between individuals with and without alcohol-dependence (AD) during a 12.5 year observation period in general hospital admissions. Methods. All comorbidities with a prevalence ≥ 1% were compared between 23,371 individuals with AD and those of 233,710 randomly selected and group-matched hospital controls of the same age and gender. Comorbidities that were risk factors for later hospital-based mortality were identified using multivariate forward logistic regression analysis. Results. Hospital-based mortality rates were 20.4 % in individuals with AD and 8.4% in controls. Individuals with AD compared to controls had a substantial excess comorbidity of physical diseases. In the AD sample 32 physical diseases contributed to the prediction of hospital-based mortality in univariate analyses and 23 physical diseases were risk factors for hospital-based mortality in multivariate analyses. All mortality risk factors had either an equal or a lower impact on hospital-based mortality in individuals with AD compared to controls. Conclusions. Physical multimorbidity is the major reason for the excess general hospital-based mortality in individuals with AD compared to controls.