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Background: Understanding the relapse risk among different illicit drugs is vital for developing an adequate relapse prevention policy. Therefore, the current study aims to explore the potential difference in long-term relapse rates between youths who use ketamine and those who use stimulants (3,4-Methylenedioxymethamphetamine [MDMA] or methamphetamine).Methods: The study's participants included 92 youths with ketamine use (ketamine group, mean age: 16.0 years) and 43 youths with MDMA/methamphetamine use (stimulants group, mean age: 16.1 years) that had undergone a family-oriented treatment program in a medical center in Taiwan. All participants were followed up for a maximum of 7 years in order to observe their long-term outcomes with regard to substance use relapse.Results: During the follow-up period, compared to the 34.8% relapse rate in ketamine users, their counterparts who used MDMA or methamphetamine had a significantly higher relapse rate (60.5%, Adjusted HR = 1.86, 95%CI: 1.06-3.28, p = 0.032). Of the youths in the ketamine group that relapsed, 65.6% continued to use ketamine in their relapse event, while 34.4% switched to MDMA or methamphetamine. Among the relapsing youths in the stimulants group, 84.6% continued to use MDMA or methamphetamine in their relapse event, while 15.4% switched to ketamine (p = 0.042).Conclusions: Compared to adolescents who use ketamine, those using MDMA or methamphetamine had higher relapse rates and were more likely to use the same type of drug upon relapsing. These results can serve as a crucial reference for developing relapse prevention policies of illicit drugs for the youth population. [ABSTRACT FROM AUTHOR]