Background: The aim of this study was to determine which predictors influence the risk of relapse among a cohort of amphetamine-type substance (ATS) users in Iran. Methods: A Cox proportional hazards model was conducted to determine factors associated with the relapse time in the Matrix treatment program provided by the Iranian National Center of Addiction Studies (INCAS) between March 2010 and October 2011. Results: Participating in more treatment sessions was associated with a lower probability of relapse. On the other hand, patients with less family support, longer dependence on ATS, and those with an experience of casual sex and a history of criminal offenses were more likely to relapse. Conclusion: This study broadens our understanding of factors influencing the risk of relapse in ATS use among an Iranian sample. The findings can guide practitioners during the treatment program.