Abstract Background Human papillomavirus (HPV) is one of the most common sexually-transmitted pathogens. A number of studies in the literature have estimated the burden of HPV-related diseases by collecting data at primary care level, while a comprehensive assessment of the global burden of HPV-related diseases on hospital resources is still lacking. Methods This was a retrospective cohort study based on hospital discharge data collected from 2000 to 2010 in the Veneto Region (north-east Italy). All hospitalizations for diseases potentially associated with HPV were identified by searching the hospital discharge records, then the proportion of these hospitalizations relating to diseases attributable to the HPV infection was calculated. Results Overall, the annual hospitalization rate for HPV-related diseases was 21.3 per 100,000 individuals in the general population, 15.8 per 100,000 males, and 27.6 per 100,000 females. Hospitalizations were due mainly to genital warts, and peak among 15- to 44-year-olds in both genders. Taking both sexes together, the hospitalizations attributable to HPV dropped from 24.5/100,000 in 2000 to 17.5/100,000 in 2011, showing a significant decline during this period, with an average annual percent change (AAPC) of −1.9% (CI 95%: -2.8, -0.9;). On the other hand, the hospitalization rate for genital warts tended to increase significantly (AAPC 3.0% [CI 95%: 1.4;4.7]), whilst there was a significantly declining trend in the hospitalization rate for anal cancer (AAPC - 5.0% [CI 95%: -7.7;-2.2]), genital cancer (AAPC −6.2% [CI 95%: -7.8;-4.6]) and oropharyngeal cancer (AAPC −4.3% [CI 95%: -4.8;-3,8]). Conclusion Data derived from the hospital records indicate that HPV-related diseases are an important public health issue.