Despite preventive health benefits of the human papillomavirus (HPV) vaccination, uptake in the United States remains low. Twenty-four states have enacted legislation regarding HPV vaccination and education. One reason these policies have been controversial is because of concerns that they encourage risky adolescent sexual behaviors. Our aim in this study is to determine if state HPV legislation is associated with changes in adolescent sexual behaviors. This is a difference-in-difference study in which we use data on adolescent sexual behaviors from the school-based state Youth Risk Behavior Surveillance System from 2001 to 2015. Sexual behaviors included ever having sexual intercourse in the last 3 months and condom use during last sexual intercourse. We compared changes in sexual behaviors among high school students before and after HPV legislation to changes among high school students in states without legislation. A total of 715 338 participants reported ever having sexual intercourse in the last 3 months, and 217 077 sexually active participants reported recent condom use. We found no substantive or statistically significant associations between HPV legislation and adolescent sexual behaviors. Recent sexual intercourse decreased by 0.90 percentage points (P = .21), and recent condom use increased by 0.96 percentage points (P = .32) among adolescents in states that enacted legislation compared with states that did not. Results were robust to a number of sensitivity analyses. Implementation of HPV legislation was not associated with changes in adolescent sexual behaviors in the United States. Concern that legislation will increase risky adolescent sexual behaviors should not be used when deciding to pass HPV legislation.