Adherence-enhancing interventions have been assessed in the literature, however heterogeneity and conflicting findings have prohibited a consensus on the most effective approach to maintain adherence over time. With the ageing population and growth of chronic conditions, evaluation of sustainable strategies to improve and maintain medication adherence long term is paramount. We aimed to determine the comparative effectiveness of interventions for improving medication adherence over time among adults with any clinical condition.Meta-analyses evaluating interventions to improve medication adherence were searched in PubMed in January 2019 and reviewed for primary studies. Experimental studies with a comparison group assessing an intervention to enhance medication adherence in adult patients with reported adherence outcomes were included. Two authors extracted data for study characteristics, interventions and adherence outcomes. Interventions were categorized into four groups or combinations: educational, attitudinal, technical and rewards. Four network meta-analyses were performed to compare interventions based on patient follow-up time. Medication adherence effect sizes were reported as odds ratios (OR) with a 95% credibility interval (CrI) and surface under the cumulative ranking curve (SUCRA) to allow ranking probabilities. Risk of bias was assessed as per Cochrane guidelines.Data was obtained from 69 meta-analyses with 468 primary studies being included in qualitative synthesis. The four networks compromised of 249 studies in total (0-3 month follow-up: 99 studies, 4-6 months: 104, 7-9 months: 18, ≥10 months: 94). Interventions showing success in follow-ups of less than 10 months varied across time. Significant effects compared to standard of care (SOC) were found in technical (4-6 months: OR 0.34, 95% CrI 0.25-0.45) and attitudinal interventions (7-9 months: 0.37, 0.17-0.84). Multicomponent interventions demonstrated effectiveness compared to standard of care with an additive effect displayed, particularly in longer follow-ups (educational + attitudinal + technical interventions ≥10 months: OR 0.49, 95% CrI 0.27-0.88).All interventions reviewed improved medication adherence compared to standard of care. Multicomponent interventions displayed the most promising results in maintenance of long-term medication adherence. Technical and reward components enhanced adherence on a short-term basis, while educational and attitudinal interventions evolved over time to be more effective in follow-ups greater than 7 months. Sustainability of adherence to medications over time is dependent upon multicomponent interventions including educational, attitudinal and technical aspects to modify and enhance patient medication-taking behavior. Future research should focus on the most cost-effective approaches able to be integrated into routine practice.