Introduction: Approximately 1 billion men and 250 million women in the world smoke, accounting for about 35% of men in high-resource countries to about 50% in developing countries [1]. The increasing trend of earlier age of smoking initiation in children and early adolescents leads to greater use in adulthood, especially in the developing world [2]. The aim of this study was to assess the prevalence of regular and frequent smoking in high school learners as well as the factors associated with cigarette use. Early identification of correlates and risk factors for cigarette use will be useful in designing intervention and prevention programmes. Methods: This cross-sectional study used a validated questionnaire to assess the extent of and factors associated with cigarette use among learners from Chatsworth high schools. Following institutional ethics approval, the study was conducted among a cluster sample of 1612 learners in grades 10 to 12 from 10 of the 18 Chatsworth public high schools. An IBM SPSS (version 20) package was used for data analysis. Crude and adjusted factors associated with regular smoking were assessed using logistic regression analysis. The cluster effect of school was dealt with by controlling for school in the analysis. A p value <0.05 was considered as statistically significant. Results are presented as odds ratios and 95% confidence intervals by gender. Results: In grades 10, 11 and 12 prevalence of regular smokers in males were 23.8%, 34.8% and 38.6%, respectively, with an overall of 30.7%, and in females 17.7%, 12.1% and 14.2%, respectively, with an overall of 15.2%. The total prevalence was 22.5%. The prevalence of frequent smokers among males by grade was 11.2%, 19.5% and 28% respectively, with an overall of 17.8% and females, 3.6%, 4.9% and 7.8%, respectively and an overall of 5%, whilst the total prevalence was 11.1%. The prevalence was significantly higher in males than females in all grades. After adjusting for school clusters and other confounders, in males there was a significant increase in risk of smoking from grade 10 through grade 12. In both genders, Zulu speaking learners were at lower risk of smoking than English speaking learners, and having a brother, sister and best friend who smokes significantly increased the risk. In females, a significant association existed between regular smoking females and having peers who smoke, as well as with having repeated a grade. Conclusion: This study showed an increase in the prevalence of cigarette smoking especially among female smokers compared with a similar study in 1993 [3]. The percentage of frequent smokers in the current study was slightly lower than in the USA (13.8%) [4]. These data warrants an urgent intervention programme to be initiated at all levels beginning at home and then at school.