We examined whether personality traits and parental education are associated with smoking initiation in a sample of Spanish secondary school students. Participants, taken from the ITACA study (842 adolescents aged 14-15 years), completed a questionnaire assessing personality traits of the Five Factor Model, smoking behaviours and parental education. Multinomial logistic regression models controlling for age and sex were used to determine the independent associations and interactions of personality traits and parental education with risk of ever trying smoking, as well as with being a regular smoker in adolescence. Higher conscientiousness was related to a lower chance of trying smoking at least once (OR = 0.57, 95% CIs = 0.46, 0.71) as well as being a regular smoker (OR = 0.39, 95% CIs = 0.27, 0.55). Higher emotional instability (neuroticism) was associated with higher risk of being in either smoking category (OR = 1.33, 95% CIs = 1.10, 1.60 and OR = 1.76, 95% CIs = 1.31, 2.35, respectively). Higher extraversion was also associated with a higher risk of both types of smoking behaviour (OR = 1.38, 95% CIs = 1.12, 1.70 and OR = 2.43 (1.67, 3.55, respectively). Higher parental education was significantly related to lower risk of being a regular smoker (OR = 0.70, 95% CIs = 0.54, 0.89), but not with trying smoking in the past. Finally, we found no evidence of the interactions between adolescents' personality and parental education in predicting adolescent smoking behaviours. We conclude that personality factors and parental education are important and independent factors associated with smoking behaviour in adolescents.