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Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassemia. However, the role that adherence to ICT plays in health-related outcomes is less well known. Our objectives were to identify adherence rates of ICT, and to assess methods of measurement, predictors of adherence, and adherence-related health outcomes in the literature published between 1980 and 2020. Of 543 articles, 43 met the inclusion criteria. Studies measured ICT adherence, predictors, and/or outcomes associated with adherence. Most studies were across multiple countries in Europe and North America (n = 8/43, 18.6%), recruited in clinics (n = 39/43, 90.7%), and focused on β-thalassemia (β-thal) (n = 25/43, 58.1%). Common methods of assessing ICT adherence included patient self-report (n = 24/43, 55.8%), pill count (n = 9/43, 20.9%), prescription refill history (n = 3/43, 7.0%), provider scoring (n = 3/43, 7.0%), and combinations of methods (n = 4/43, 9.3%). Studies reported adherence either in 'categories' with different levels of adherence (n = 24) or 'quantitatively' as a percentage of doses of medication taken out of those prescribed (n = 17). Adherence levels varied (median 91.7%, range 42.0–99.97%). Studies varied in sample size and methods of adherence assessment and reporting, which prohibited meta-analysis. Due to a lack of consensus on how adherence is defined, it is difficult to compare ICT adherence reporting. Further research is needed to establish guidelines for assessing adherence and identifying suboptimal adherence. Behavioral digital interventions have the potential to optimize ICT adherence and health outcomes. [ABSTRACT FROM AUTHOR]