This aim of this study was to evaluate the prevalence of human papillomavirus (HPV) infections among women (aged 15–55 years) in four of the biggest cities and regions in Bulgaria (viz., Sofia, Plovdiv, Varna, and Burgas), as well as in two other smaller cities (viz., Pleven and Vidin). Furthermore, study aimed to identify the prevalence of the 12 high-risk HPV (HR-HPV) genotypes in 2012, and to predict the benefits of a future national vaccination campaign for 12-year-old girls in Bulgaria. This HPV genotypes prevalence study covered 2,331,341 women from these cities and regions, representing 61.7% of the female population of Bulgaria. DNA-sorb-AM nucleic acid extraction kit was used to analyze the HPV status in cervical samples collected during a 4-year period (2008–2011) from 1,120 women aged 15–55 years (divided into four age groups) who had visited 47 gynecological clinics across the study sites. HR-HPV infections were confirmed in 435 (38.8%) of the women examined. The remaining 685 (61.2%) women were found to be HR-HPV negative. The most common genotype in all 435 infected women was HPV16, which was found in 200 women (46%), followed by HPV56 in 86 women (19.8%), HPV31 in 53 women (12.2%), and HPV33 in 50 women (11.5%). This is the first study to have established the prevalence of HR-HPV infections in the larger Bulgarian regions and cities (including the capital), and to have drawn attention to the unusually high proportion of the different HR-HPV genotypes. J. Med. Virol. 85:1577–1584, 2013. © 2013 Wiley Periodicals, Inc.