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INTRODUCTION Tobacco smoking is the largest preventable cause of global mortality, with its prevalence increasing in Sub-Saharan Africa, particularly among adolescents. We sought to determine the factors associated with tobacco smoking among Nigerian school adolescents and investigate the interaction between school location and socioeconomic status (SES). METHODS Using a cross-sectional study design, 4332 eighth to tenth grade students in rural and urban secondary schools in Enugu State, Nigeria, were selected by stratified two-stage cluster sampling. We collected data using a modified Global Youth Tobacco Survey (GYTS) Core Questionnaire. Outcome measures were current smoking of cigarettes and other smoked tobacco. Multilevel mixed effects logistic regression models were used to determine factors associated with current tobacco smoking and were considered statistically significant at p<0.05. RESULTS Prevalences of current smoking of cigarettes and other smoked tobacco were 13.3% (95% CI: 11.3--15.7) and 5.8% (95% CI: 4.6--7.2), respectively. Possession of higher weekly allowance, exposure to secondhand smoke or tobacco advertisements, having smoking parents, friends or classmates who smoke, and sale of cigarettes near school, were positively associated with current smoking of tobacco. Female sex, having both parents employed and being exposed to tobacco teaching in school were negatively associated with current cigarette smoking while increasing age and high father's SES were negatively associated with current smoking of other tobacco products. There was an interaction between school location and father's SES in the association with cigarette smoking. The higher odds of smoking in rural versus urban schools were much higher for students with fathers of high SES compared to low SES. In rural schools, high SES was associated with higher odds of smoking, but in urban schools low SES was associated with higher odds of smoking. CONCLUSIONS Environmental factors are associated with adolescent tobacco smoking. Tobacco control programs should use targeted strategies that vary depending on the local context. [ABSTRACT FROM AUTHOR]