Opioid use disorder (OUD) is associated with a high risk of premature death. Medication-assisted treatment (MAT) is the primary treatment for opioid dependence. We comprehensively assessed the effects of different MAT-related characteristics on mortality among those with OUD by a systematic review and meta-analysis. The all-cause and overdose crude mortality rates (CMRs) and relative risks (RRs) by treatment status, different type, period, and dose of medication, and retention time were pooled using random effects, subgroup analysis, and meta-regression. Thirty cohort studies involving 370,611 participants (1,378,815 person-years) were eligible in the meta-analysis. From 21 studies, the pooled all-cause CMRs were 0.92 per 100 person-years (95% CI: 0.79-1.04) while receiving MAT, 1.69 (1.47-1.91) after cessation, and 4.89 (3.54-6.23) for untreated period. Based on 16 studies, the pooled overdose CMRs were 0.24 (0.20-0.28) while receiving MAT, 0.68 (0.55-0.80) after cessation of MAT, and 2.43 (1.72-3.15) for untreated period. Compared with patients receiving MAT, untreated participants had higher risk of all-cause mortality (RR 2.56 [95% CI: 1.72-3.80]) and overdose mortality (8.10 [4.48-14.66]), and discharged participants had higher risk of all-cause death (2.33 [2.02-2.67]) and overdose death (3.09 [2.37-4.01]). The all-cause CMRs during and after opioid substitution treatment with methadone or buprenorphine were 0.93 (0.76-1.10) and 1.79 (1.47-2.10), and corresponding estimate for antagonist naltrexone treatment were 0.26 (0-0.59) and 1.97 (0-5.18), respectively. Retention in MAT of over 1-year was associated with a lower mortality rate than that with retention ≤1 year (1.62, 1.31-1.93 vs. 5.31, -0.09-10.71). Improved coverage and adherence to MAT and post-treatment follow-up are crucial to reduce the mortality. Long-acting naltrexone showed positive advantage on prevention of premature death among persons with OUD.