Self-sampling by cervicovaginal lavage could be an attractive method to detect high-risk human papillomavirus (hr-HPV) infections to identify women with a risk of cervical precancer. The objective of our study was to use self-sampling for the first time in a cross-sectional approach to determine HPV prevalence and genotype distribution. We evaluated participants' acceptance and laboratory results from self-obtained samples versus endocervical brush samples obtained by gynecologists. To determine the sensitivity of both sampling methods in presumed high- and low-prevalence settings, two groups of women 20 to 30 years of age with (n = 55) and without (n = 101) a recent suspicious cytological smear were compared. Overall, 76% (95% confidence interval [95% CI], 65 to 88) of women with and 40% (95% CI, 30 to 49) of women without a recent suspicious cytological smear tested HPV positive. The prevalences of high-risk HPV strains were 71% (95% CI, 59 to 83) and 32% (95% CI, 22 to 41), respectively, for these two groups. The agreement for hr-HPV between the two sampling methods for women with and without suspicious cytology was 84% (κ = 0.65; 95% CI, 0.44 to 0.86) and 91% (κ = 0.78; 95% CI, 0.64 to 0.92), respectively. Participants rated the user-friendliness of the self-sampling method on a visual analog scale from 0 (easy) to 100 (difficult) with a median of 12. In conclusion, self-sampling by cervicovaginal lavage is a reliable method to determine hr-HPV prevalence and is well accepted by young adult females.