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Most sexually active people will be infected with a sexually transmitted infection (STI) at some point in their lives. The number of STIs in the United States was previously estimated in 2000. We updated previous estimates to reflect the number of STIs for calendar year 2008.We reviewed available data and literature and conservatively estimated incident and prevalent infections nationally for 8 common STIs: chlamydia, gonorrhea, syphilis, herpes, human papillomavirus, hepatitis B, HIV, and trichomoniasis. Where available, data from nationally representative surveys such as the National Health and Nutrition Examination Survey were used to provide national estimates of STI prevalence or incidence. The strength of each estimate was rated good, fair, or poor, according to the quality of the evidence.In 2008, there were an estimated 110 million prevalent STIs among women and men in the United States. Of these, more than 20% of infections (22.1 million) were among women and men aged 15 to 24 years. Approximately 19.7 million incident infections occurred in the United States in 2008; nearly 50% (9.8 million) were acquired by young women and men aged 15 to 24 years. Human papillomavirus infections, many of which are asymptomatic and do not cause disease, accounted for most of both prevalent and incident infections.Sexually transmitted infections are common in the United States, with a disproportionate burden among young adolescents and adults. Public health efforts to address STIs should focus on prevention among at-risk populations to reduce the number and impact of STIs.