Objective: Adolescents are exposed to a wide range of high-risk health behaviors. This study aimed to investigate the high-risk health behaviors of adolescents in an Iranian adolescent population and gender differences., Method: This cross-sectional descriptive study recruited high school students in Yazd city in center of Iran. Schools were randomly selected. In each school, all selected classes were included. Sampling in each class was census. The study investigated self-reported high-risk health behaviors. Students completed the Global School-based Student Health Survey (GSHS), an anonymous, validated questionnaire., Results: 2420 students participated in this study (52.5% male). The age range was 12-19 years. Daily consumption of ≥1 serving of fruit and vegetables per day was reported by 77.4% and 49.5% of respondents, respectively. Adequate physical activity was reported by only 18.4% of adolescents, and significantly less frequently by girls than boys (p < 0.001). 11.8% were current smokers (M/F ratio: 2.6), and 20.5% (M/F ratio: 1.5) were ever used hookah. The prevalence of ever alcohol and substance abuse was 15.5% and 8.8%, respectively. The prevalence of tobacco and substance use was significantly higher in participants' boys than in girls (p < 0.001). Males were over twice more likely to report frequent fighting in the past 12 months than girls. Overall, girls reported more parental supervision than boys (82.1% vs. 73.4%) and parental monitoring (90.6% vs. 86.8%), while boys reported higher levels of awareness over leisure activities than girls (65.8% vs. 58.4%)., Conclusions: High-risk health behaviors are more common in boys than girls. Health policymakers should use these results in prioritizing and designing health interventions to promote youth health. Further studies are recommended to identify the factors influencing the prevalence of these behaviors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 Published by Elsevier Ltd.)