Aims: To investigate the prevalence, persistence and risk factors of high oncogenic risk human papillomavirus (HPV) among urban and rural women of reproductive age coming to consult a gynaecologist. Methods: A prospective cohort study in urban (Kaunas) and rural (Marijampole) regions of Lithuania. The data were collected in 8 healthcare institutions from women seeking consultation of gynaecologists using a questionnaire for finding out demographic, social, behavioural and biomedical factors. HPV DNA was determined by molecular hybridization method (hybrid capture version II) determining HPV of high oncogenic risk. Result: 1,120 women participated in the study. The prevalence of high-risk HPV among the studied women was 25.1%. It was higher among the urban women than among the rural women. The prevalence of high-risk HPV was increased if the subjects had 2 or more sexual partners during the last 12 months (OR 2.81; 95% CI 1.83–4.32), were 19 years of age or younger (OR 2.68; 95% CI 1.47–4.91), were smoking (OR 1.81; 95% CI 1.16–2.81), and had secondary or lower education level (OR 1.43; 95% CI 1.01–2.04). This infection was obviously associated with high- and low-grade squamous intraepithelial changes of the cervix (OR 1.66, 95% CI = 1.08–2.53). Conclusion: The incidence rate for cervical cancer in Lithuania is one of the highest in comparison with other European countries. HPV infection was also particularly common in the studied population. About one-fourth of the women were infected with high-risk HPV infection. Young and less educated women were found to be the group that was most exposed to HPV, and therefore public health interventions and education seem to be essential in programs aimed at reducing the incidence of cervical cancer.