Human papillomavirus (HPV) types cause approximately 70% of cervical cancer worldwide. Two vaccines have been recently evaluated in randomized controlled trials: the bivalent vaccine for HPV 16 and 18 (Cervarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) and the quadrivalent vaccine for HPV 6, 11, 16, and 18 (Gardasil, Merck and Co, Inc, Whitehouse Station, NJ). We have performed a systematic review of all randomized controlled trials in which vaccines against HPV were compared with placebo regarding efficacy, safety, and immunogenicity. Six studies met the inclusion criteria, which included 47,236 women. The first objective in this systematic review was to assess vaccine efficacy in the prevention of cytologically and/or histologically proven lesions. And the secondary objective was the evaluation of safety and vaccine immunogenicity. Bivalent and quadrivalent HPV vaccines significantly reduced the rate of lesions in the cervix, vulva, vagina, and anogenital region, with efficacy of 93% (95% confidence interval [CI], 87-96) and 62% (95% CI, 27-70), respectively, when compared with the control groups according to intention to treat. Regarding safety, we found more symptoms in the bivalent vaccine group (35%; 95% CI, 5-73) when compared with the control groups. In regard to vaccine immunogenicity, there was seroconversion in the group that received the vaccine when compared with the placebo group in the bivalent and quadrivalent vaccines. Prophylactic vaccination can prevent HPV infection in women aged 9 to 26 years not previously infected with the HPV subtypes covered by the vaccines. To evaluate cervical cancer incidence and mortality, a longer follow-up is necessary.