BACKGROUND: The most recent estimates of the number of prevalent and incident sexually transmitted infections (STIs) in the United States were for 2008. We provide updated estimates for 2018 using new methods. METHODS: We estimated the total number of prevalent and incident infections in the United States for 8 STIs: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, human papillomavirus, sexually transmitted hepatitis B, and sexually transmitted HIV. Updated per-capita prevalence and incidence estimates for each STI were multiplied by the 2018 full resident population estimates to calculate the number of prevalent and incident infections. STI-specific estimates were combined to generate estimates of the total number of prevalent and incident STIs overall, and by sex and age group. Primary estimates are represented by medians, and uncertainty intervals are represented by the 25th (Q1) and 75th (Q3) percentiles of the empirical frequency distributions of prevalence and incidence for each STI. RESULTS: In 2018, there were an estimated 67.6 (Q1, 66.6; Q3, 68.7) million prevalent and 26.2 (Q1, 24.0; Q3, 28.7) million incident STIs in the United States. Chlamydia, trichomoniasis, genital herpes, and human papillomavirus comprised 97.6% of all prevalent and 93.1% of all incident STIs. Persons aged 15 to 24 years comprised 18.6% (12.6 million) of all prevalent infections; however, they comprised 45.5% (11.9 million) of all incident infections. CONCLUSIONS: The burden of STIs in the United States is high. Almost half of incident STIs occurred in persons aged 15 to 24 years in 2018. Focusing on this population should be considered essential for national STI prevention efforts.