BackgroundThe prevalence of substance use among secondary school children in Nasarawa State, North-Central Nigeria, is unknown. ObjectiveTo provide comprehensive prevalence estimates of substance use and associated factors among in-school adolescents in Nasarawa, Nigeria. Methods A cross-sectional, multi-stage survey was conducted among 1600 students in 26 schools. Students completed a self-administered questionnaire regarding socio-demographics and substance use habits. The questionnaire was adapted from a standardized questionnaire. ResultOf the 1518 who completed the questionnaire, there were more boys (51.3%) than girls. Most participants were 16-18 years old (55.3%), attending non-residential (70%), private (54.4%), and mixed-sex schools (79.3%). Most were Christians (83.4%) and from monogamous families (73.2%). The prevalence of ever-tried cigarette smoking was 14.8%, marijuana (13.6%), and inhalants (12.9%). Students > 18 years were more likely to ever try cigarette smoking (aOR 1.88, 95%CI 0.99-3.58), tried during the last 12 months (aOR 2.29, 95%CI 1.18-4.46), and tried during the last 30 days (aOR 2.41, 95%CI 1.12-4.84) than those younger. Students whose either parent smoked were more likely to ever try cigarette smoking (aOR 9.9, 95%CI 6.95-14.23), marijuana (aOR 9.74, 95%CI 6.78-13.99), inhalants (aOR 7.27, 95%CI 5.04-10.50), and other psychoactive substances (aOR 9.25, 995%CI 6.53-13.11) than students whose parents do not. Substance usage was influenced by factors such as being Muslim and in SS1 class, attending a public and non-residential school, coming from polygamous homes, and living with single parents. ConclusionSecondary school students in Nasarawa State exhibit variable substance use behaviors, influenced by socio-demographic factors, requiring consideration in substance use interventions.