Few studies have examined the long-term efficacy of computer-based smoking prevention and cessation programs. We analyzed the long-term impact of A Smoking Prevention Interactive Experience (ASPIRE), a theoretically sound computer-based smoking prevention and cessation curriculum for high school students. Sixteen predominantly minority, inner-city high schools were randomly assigned to receive the ASPIRE curriculum or standard care (receipt of the National Cancer Institute's Clearing the Air self-help booklet). A total of 1160 students, 1098 of whom were nonsmokers and 62 smokers at baseline, were included. At 18-month follow-up, among baseline nonsmokers, smoking initiation rates were significantly lower in the ASPIRE condition (1.9% vs. 5.8%, p<.05). Students receiving ASPIRE also demonstrated significantly higher decisional balance against smoking and decreased temptations to smoke. Differences between groups in self-efficacy and resistance skills were not significant. There was a nonsignificant trend toward improved smoking cessation with ASPIRE, but low recruitment of smokers precluded conclusions with respect to cessation. ASPIRE demonstrated the potential for an interactive multimedia program to promote smoking prevention. Further studies are required to determine ASPIRE's effects on cessation.