Relapse is an inevitable part of recovery from substance use such that polysubstance users have high chances of relapse (Andreas et al., 2015). In Pakistan, approximately 70% of people with substance use have history of relapse (Masood & Sahar, 2014). Actively changing substance use behavior have a protective effect against relapse (Hartney, 2020) which is basic component of personal growth initiative (Robitschek, 1998). The overall personal growth initiative however has not yet studied in this context. The present study thus aimed to assess relationship of personal growth initiative and chances of relapse along with the moderating role of polysubstance use for this relationship. Personal Growth and Initiative Scale-II-Urdu (Zaman & Naqvi, 2020) and Advance Warning of Relapse (AWARE-Urdu) Questionnaire (Sahar & Naqvi, 2021) were administered on sample of people with substance use (N = 240) ranging in age from 20-60 years. The sample was recruited from rehabilitation centers within Islamabad and Rawalpindi. Findings demonstrate that personal growth initiative negatively associates and explains 15% variance in chances of relapse. Results from moderation analysis suggest that the interaction effect for polysubstance use and personal growth initiative explains about 5% of variance in chances of relapse (ΔR2 = .05) such that, significant decrease in chances of relapse is observed with increasing personal growth initiative among the drug addicts with lower polysubstance use. It was found that the most commonly used drugs among the sample were cannabis (n = 109), cocaine (n = 74), and alcohol (n = 67). These findings could help address relapse among drug addicts.