Background: Substance use disorders (SUDs) often involve cycles of relapse. Prevention of relapse is the primary goal for effective treatment. Motivational Enhancement Therapy (MET) offers a client-centered approach to address these internal barriers to prevent treatment prematurely potentially before completing detoxification recovery. This study aimed to assess the effect of Motivational Enhancement Therapy on Probability of Relapse, among Clients with Substance Use Disorders. Methods: A quasi-experimental study was conducted on a convenient sample of 60 clients with SUDs at El-Maamoura Hospital for Psychiatric Medicine in Alexand6ria. Tools: The Sociodemographic and Clinical Data Structured Interview Schedule and The Advance Warning of Relapse Scale were used. Results: There was a statistically significant improvement in the total score of the probability of relapse Scale at post-intervention and maintained at 3 months of follow-up (55.52 SD=7.42, 68.67 SD=7.13, 68.74 SD=7.24, respectively), with a large effect size of 90.2%. Conclusions: Motivational Enhancement Therapy was found to be effective in reducing the probability of relapse among clients with SUDs. MET was found to improve treatment adherence,