Introduction and Aims. Over recent years, numerous school-based preventive strategies have been explored as possible options to address illicit drug use by young people. However, there is scope to extend current knowledge of which school students are most at risk of illicit drug-related harm. To investigate potential differential risk, the prevalence and patterns of illicit drug use of Australian secondary school students were examined according to demographic, school, economic and licit drug use factors. Design and Methods. Analyses were conducted on the 2005 Australian Secondary Students' Alcohol and Drug survey. A total of 21805 secondary school students aged 12-17years from 376 schools completed the pencil and paper classroom questionnaire. Results. The greatest risk factors for students using illicit drugs were tobacco and alcohol use. Students with self-rated below average academic achievement, with more than $20 a week of disposable income, and who were Indigenous were more likely to report illicit drug use. Discussion and Conclusions. While causal pathways could not be examined in the current data, and these relationships are likely to be complex and multi-directional, the findings indicate potentially at-risk populations who warrant extra support to address illicit drug-related harm.