OBJECTIVES: Low medication adherence is a serious, but preventable, issue facing health care services today. Although health care providers are accountable to provide appropriate information to patients regarding their medication treatment, patients’ ability to understand the information in the process of provider-patient communication has been overlooked. Using a systematic literature review and subsequent meta-analysis, this study evaluates the impact of health literacy as a predictor of medication adherence among patients with chronic diseases. METHODS: Articles were identified through literature searches conducted on MEDLINE, PUBMED, CINAHL, PsycInfo, International Pharmaceutical Abstracts, Web of Sciences, and review of reference citations. Methodological variables, effect sizes of associations, diseases, and measures of health literacy and medication adherence were abstracted from each eligible article. Studies were categorized by disease category, statistical methods and significance (bivariate or multivariate significance and insignificance), literacy and adherence outcome metrics. The population effect size of the association between health literacy and medication adherence are estimated based on simulation based meta-analysis. RESULTS: Across 29 studies, 47% multivariate studies and 80% bivariate studies reported that higher health literacy levels were statistically significantly associated with better adherence to prescribed medications. There was wide variation on the association between health literacy and medication adherence across diseases. For example, 75% of studies on diabetes reported no statistical associations between health literacy and medication adherence, while 100% of studies on glaucoma reported statistical associations. The Monte Carlo simulation based meta-analysis found that a statistically significant association between health literacy and medication adherence (p<0.001), although the unweighted population effect size is relatively small (r=0.122 with a 95% confidence interval of (0.0849, 0.159). CONCLUSIONS: Health literacy is a proven predictor of medication adherence, and it is more potent in some diseases than others. Adherence intervention may focus on patients’ health literacy in the provider-patient communications and health information exchange.