AbstractObjectivesThis study aimed to estimate the extent of smoking experience among high and middle school adolescents in Southern Tunisia and to delineate its potential associated factors.MethodsWe conducted a cross-sectional study among middle and high school-adolescents in the governorate of Sfax, South of Tunisia in the 2017–2018 school-years. A questionnaire was anonymously administered to a representative sample of 1,210 school-adolescents randomly drawn.ResultsThe mean age of the school-adolescents was 15.6 ± 4.2 years. The prevalence of lifetime smoking was 16.7% (95% CI=[14.7–18.8%]) (boys 32.6%; girls 5.9%;p<0.001). Among the respondents, 13.9% (95% CI=[11.9–15.8%]) were current smokers. In multivariate logistic regression analysis, independent associated factors of current smoking were male gender (Adjusted (AOR)=10.2; p<0.001), 16–17 and 18–19-year age-groups (AOR=2; p=0.005 and AOR=2.6; p=0.001, respectively), below average academic performance (AOR=5.2; p=0.012), divorced parents (AOR=3.9; p=0.007), family monthly income ≥800 dollars (AOR=2.1; p=0.001), having a part time job (AOR=3.9; p<0.001) and a perceived high stress level (AOR=1.98; p=0.008). Secondhand smoke (AOR=1.8; p=0.011) and concomitant alcohol drink (AOR=14.56; p<0.001) were independent predictors of current smoking, while high education level of the father was independently associated with lower prevalence of current smoking (AOR=0.17; p<0.001).ConclusionThe prevalence of lifetime and current smoking were relatively high in Southern Tunisian middle and high schools. Multilevel influences on youth smoking behavior had been identified, which reflected the need to conceive appropriate school interventions and effective antismoking education program.