Background. Smoking may increase the risk of cervical cancer, a disease that is related to human papillomavirus (HPV) infection. However, the effects of smoking on the natural history of HPV are poorly understood, especially in women coinfected with human immunodeficiency virus (HIV).Methods. HIV-infected (n=1797) and HIV-uninfected (n=496) women were assessed every 6 months for type-specific HPV DNA. Smoking status was self-reported. Covariates included age, parity, sexual behavior, HIV load, CD4(+) T cell count, and antiretroviral therapy.Results. Smoking was positively associated with HPV prevalence at baseline in HIV-infected women (P=.002) and was significantly associated with type-specific HPV detection (e.g., type 18, odds ratio [OR], 2.45; 95% confidence interval [CI], 1.86-3.22). In Cox models, detection of HPV was significantly associated with smoking in HIV-infected women (relative hazard [RH], 1.33; 95% CI, 1.10-1.60; P=.003), but HPV persistence was not (RH, 0.97; 95% CI, 80-1.16; P=.72). The overall likelihood of acquiring persistent HPV was higher in smokers (OR, 1.39; 95% CI, 1.05-1.86; P=.023) because of greater incidence.Conclusions. Among HIV-infected women, smoking is associated with a significantly higher prevalence and incidence of HPV infection. Smoking during HIV infection may alter the natural history of HPV infection and increase the risk of cervical disease.