Personality is one of several factors that have been related to the initiation, maintenance and cessation of smoking. This paper aims to analyze the relationship between the alternative five-factor model of personality (AFFM), nicotine dependence (ND), nicotine use (NU) and cessation after twelve months of a cognitive-behavioral therapy combined with medication. In this prospective study, a sample of 103 smokers who were taking part in a workplace smoking cessation intervention, answered the Zuckerman-Kuhlman Personality Questionnaire. ND and NU were measured with the Fagerström Test for the Nicotine Dependence (FTND) and the number of cigarettes smoked per day (CPD), respectively. Tobacco cessation was self-reported at twelve months follow-up and biologically confirmed. Results varied according to gender. In men, low scores on Sociability predicted high ND and large number of CPD. In addition, low scores on Sensation Seeking and high scores on Impulsivity predicted also a high smoking rate at baseline. No personality traits were found to explain ND in women, but high Impulsivity-Sensation Seeking and General Activity predicted high CPD. Predictors of cessation also differed by gender. Apart from FTND level, high levels on Impulsivity predicted relapse in males. In women, high levels on Sociability predicted relapse. This model correctly classified two thirds of abstainers and relapsers for men and three fourths for women at 12months. Furthermore an interaction between personality and gender was observed. The AFFM appears to have a substantial power for predicting cessation. Personality assessment when beginning treatment for smoking cessation could allow incorporating strategies to improve outcomes.