Determinants of genital human papillomavirus (HPV) persistence in 393 women initially cytologically normal were investigated by testing them for HPV DNA twice over amedian interval of 14.9 months. At each visit, interview information was obtained and acervicovaginal lavage sample was collected for polymerase chain reaction-based HPV testing. Twenty-six percent of the women were HPV-positive at the first sampling. Data on HPV type was available for 86 HPV-positive women (84%); 35 of these women (41%) had persistent type-specific HPV detection. Persistence decreased with time between samplings. Women aged ≥30 years had a higher percentage of persistence (65%) than those ≤24 years (32%, P =.02). The percentage of persistencewas higher amongwomen infected with HPV types known to be cancer-associated (45%) than among those infected with other types (24%, P =.11). These findings wereindependent of each other andof timing between samplings. Although based on a prevalentcohort, these results are concordant with previous suggestions that HPV infection isusually transient and that cervical cancer may arise from within the subset of women with persistent HPV infection.