The purpose of this study was to examine sex differences in how the smoking behaviour of close friends and older peers at school influence smoking onset and progression among 10,843 grade 9, 10 and 11 students from 29 secondary schools in Ontario, Canada. In lower-risk student populations (i.e., students with no smoking friends or one smoking friend), males and females were both at a similar level of risk for occasional smoking as a function of the smoking rate of older students at their school. Among higher-risk student populations (i.e., students with three or more close friends who smoke), the smoking rate of older students at school did not influence the risk of occasional smoking. The odds of a female student being a regular smoker increased as the prevalence of smoking among older students at her school increased regardless of her close friends' smoking behaviour. However, among male students, the influence of older student smoking at school on the odds of regular smoking was moderated by the number of close friends who smoke. It appears that the prevalence of older student smoking at a school is more influential among younger female students, whereas the smoking behaviour of close friends appears to be more influential among younger male students. This new finding provides unique insight for tailoring and targeting future school-based smoking prevention initiatives.