Methamphetamine (ab)use have gained popularity among youth and is increasingly become a part of mainstream culture. Methamphetamine(ab)use is dangerous because of its wide range adverse outcomes and hazardous sustaining side effects. Its dependence is hardly withdrawn by routine therapeutic methods. This study is devoted to evaluate the efficacy of Regulated 12-Session Matrix Model in outpatient methamphetamine-dependent individuals. 24 individuals were chosen according to inclusion/exclusion criteria of the study and randomly assigned to equal experimental (age range 19-41; mean age: 46.9) and control groups (age range: 21-42; mean age: 27.8). Experimental group members partook Regulated 12-Session Matrix Model once a week in 12 consecutive weeks, while control group members remained at waitlist. Independent t-test in 12th week showed that experimental group had lower methamphetamine use, comparing to control group (p<.05).Phillai’s Trace, Wilk’s Lambda, Hotelling- Lawley's trace, and Roy's largest root showed that there are significant association between experimental and control groups in reduction of methamphetamine-use lapse (p<.05).Within-subject F ratio revealed that “methamphetamine use” was significantly reduced in experimental group after clinical intervention (p<.001). Findings of the study indicate the efficacy of Regulated 12-Session Matrix Model in craving management and control as well as reduction of lapse and substance (ab)use in methamphetamine-dependent patients. It appears that the Regulated 12-Session Matrix Model would be a new reliable solution to treat methamphetamine-dependence in Iran and other alike cultural and social atmospheres. Limitations and future implications are discussed.