This study investigated involvement in substance use and sexual activities among adolescents in Cape Town, and specifically the associations between methampethamine use and sexual risk behaviours. Data were collected from 15 randomly selected and 15 matched schools in Cape Town via quantitative questionnaires. Students used hand-held computers (PDAs) to answer the questions. A total of 4605 grade 9 students were sampled. Male and female students were almost equally likely to have used methamphetamine at least once (13% versus 12%). Students who had used methamphetamine in the past 30 days were significantly more likely to have had vaginal, anal or oral sex than students who had never used it, to have been pregnant/been responsible for a pregnancy and to have been diagnosed with a sexually transmitted infection. Logistic regression analysis indicated significant associations between methamphetamine use in the past 12 months and engaging in vaginal and anal sex. Drug abuse and sexually transmitted infections (STI) prevention services should incorporate the link between drugs and STI into their prevention and education strategies, especially those aimed at school-going adolescents.