Objectives: To systematically review published randomized controlled trials (RCTs) assessing the efficacy of MI to support medication adherence in adults with chronic conditions. Methods: A systematic review (PROSPERO-CRD42020025374) was performed by searching in Pubmed/MED-LINE, PsycINFO, The Cochrane Library and Web of Science. Studies were included for the following: RCTs assessing the impact of MI on medication adherence among adults with chronic diseases. Two reviewers con-ducted independent screening of records and full-text articles published until July 2020. Quality was assessed with the Risk of Bias 2 tool for RCTs. Results: From 1262 records identified, 54 RCTs were included. The MI interventions were delivered alone or in combination with other interventions, and varied in mode of delivery (e.g. face-to-face, phone), exposure level (duration, number of sessions), and provider characteristics (profession, training). Most interventions were developed in infectious diseases (n = 16), cardiology (n = 14), psychiatry (n = 8), and endocrinology (n = 7). Medication adherence showed significant improvement in 23 RCTs, and other clinical outcomes were improved in 19 RCTs (e.g. risky behaviors, disease symptoms). Conclusions: MI is an approach to medication adherence support with an increasing evidence base in several clinical domains and further potential for adaptation to different settings. Practice implications: In further studies, particular attention should focus on methodological issues such as the populations of patients to include - patients with suboptimal adherence, the evaluation of fidelity to the MI spirit and components, and a sound measurement of medication adherence and clinical outcomes.