Background: Many sexually transmitted diseases (STDs) are prevalent among adolescents, get compliance to undergo STD testing by this population is suboptimal, Efforts to enhance compliance with testing among at-risk youth are needed. Goal: To determine the feasibility and acceptability of self-collection of vaginal swabs for the detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis among high-school students attending a school health clinic. Study Design: Enrolled in the study were 228 female students between the ages of 15 and 19 years. Each student self-collected a single vaginal swab that was tested for C trachomatis, N gonorrhoeae, and T vaginalis by polymerase chain reaction amplification, Acceptability of self-collection of vaginal swabs was assessed. Results: The prevalence of any STD was 18%, Trichomoniasis, chlamydia, and gonorrhea were diagnosed in 10%, 8%, and 2% of students, respectively, Nearly 13% of females who had never previously had a gynecologic examination tested positive for an STD, and 51% of infected students would not have pursued testing by traditional gynecologic examination if self-collection was not offered. Self-collection of vaginal swabs was almost uniformly reported as easy to perform (99%) and preferable to a gynecologic examination (84%), Nearly all (97%) stated that they would undergo testing at frequent intervals if self-testing were available. Conclusions: Self-collected vaginal swabs for STD testing can be easily implemented in a high-school setting with high acceptability among students, enabling the detection of many STDs that would otherwise remain undetected and untreated.