BackgroundSince smoking is a major public health problem among Tunisian teenagers, it is important to identify the underlying risk and protective factors associated with initiation of this behavior. MethodsA cross-sectional, school-based survey of students was conducted by the Tunisian Ministry of Health among a nationally representative sample of 4172 adolescents aged between 12 and 20years attending public, private, and professional secondary schools across Tunisia who participated in the Survey of the Health of Tunisian adolescents in 2000. For data analysis, we first calculated crude odds ratios (OR) followed by calculating adjusted OR after using multivariate logistic regression models. ResultsAlmost one-third of respondents had already started smoking at an average age of 13 years, 6.4% among them smoked daily. Demographic vulnerabilities to smoking behavior were gender (boys more than girls), age and residence in urban areas and particularly in Greater Tunis and the North East. Familial and school factors were parental divorce, poor relationship with parents, poor integration into the peer group, and poor school investment. Psychological and behavioral factors were low self-esteem level and the occurrence of stressful life events, risk taking and alcohol consumption when there was no association with the depression, anxiety and body image. Protective factors against the experimental cigarettes were mainly sports and reading. ConclusionThere are many factors associated with smoking behavior among adolescents. All of these predictors need to be considered in smoking prevention among Tunisian teenagers.