BACKGROUND: Sexually transmitted infections (STIs) are common in adolescents worldwide. Vulnerability to STIs increases with risky sexual practices. This study described the sexual practices, estimated the prevalence of STIs, and identified correlates associated with STIs among participants, enrolled in public high schools, in the District of Panama, Panama. METHODS: A cross sectional study, using multistage cluster sampling, was conducted among participants, aged 14-18 years, enrolled in public high schools, in the District of Panama, Panama City, Panama, from August to November, 2015. Participants completed a self-administered questionnaire and provided biological samples. The samples of those reporting sexual activity (oral, vaginal, and/or anal intercourse) were tested for STIs. Odds ratios were used to identify correlates of STIs in this population. RESULTS: A total of 592 participants were included, of whom, 60.8% reported a history of sexual activity, and 24.4% tested positive for least one STI. STIs were more common in female participants, (33.5%). Compared to those without STIs, higher proportions of those with at least one STI reported ≥3 sexual partners in their lifetime (60.0%) and current sexual activity (76.3%). In the multivariable model, correlates of STI included female participants (Adjusted Odds Ratio (AOR) = 5.8, 95% Confidence Interval (CI) 2.3-14.6) and those who engaged in sexual intercourse with casual partners (AOR = 3.0, 95% CI: 1.2-7.5). CONCLUSIONS: We report a high STI prevalence among adolescents attending public high schools, in the District of Panama. Reported risky sexual practices were common and correlated with STIs. Female participants and those reporting sexual intercourse with casual partners were more likely test positive for at least one STI. Our study identified a need for effective interventions to curb future infections in this population.