Background: This comprehensive systematic review and meta-analysis were performed to assess the associated factors of maintenance in patients with methadone therapy in the world.Methods: A systematic literature review was performed from several scientific databases; these include PubMed, Scopus, ISI Web of Science, and MEDLINE. We searched the following keywords: “Methadone”, “Maintenance”, “Retention”, “Meta-analysis” and “Associated factors”. Data were selected based on the inclusion and exclusion criteria. The purpose of this study was to assess the associated factors of maintenance in patients under treatment with methadone by an overall effect size, odds ratio (OR) [95% confidence interval (CI)] using meta-analysis.Findings: We selected 24 researches out of 94413 for our study based on the inclusion and exclusion criteria for systematic review and meta-analysis. The pooled recognized five significant positive associations of age, marital status, employment status, gender, and length of treatment with methadone usage (OR age = 3.566, 95% CI = 3.296-3.836, P < 0.001; OR marital status = 1.101, 95% CI = 1.028-1.175, P = 0.025; OR employment = 1.157, 95% CI = 1.060-1.254, P = 0.015; OR gender = 4.686, 95% CI = 4.434-4.939, P < 0.001; OR duration of treatment = 1.543, 95% CI = 1.443-1.647, P < 0.001; respectively). However, education and injection status showed a non-significant positive association with methadone usage (OR education level = 1.279, 95% CI = 0.976-1.583, P = 0.266; OR injection status = 1.205, 95% CI = 0.725-1.658, P = 0.442).Conclusion: This systematic-review and meta-analysis study displayed that factors such as age, marital and employment status, gender, and duration of treatment are effective on maintenance in patients under treatment of methadone.