BACKGROUND: Various aspects of medication adherence and health-related quality of life (HRQOL)have been studied in subjects with COPD. Nevertheless, little is known about the association between these factors. The aim of this study was to undertake a systematic review of the published literature focusing on the relationship between medication adherence and HRQOL in COPD. METHODS: A systematic literature search of English language articles was conducted in April 2013 using MEDLINE. No publication date limits were defined. All of the included studies were assessed for quality. RESULTS: Seven studies were included in the review. Three of the assessed studies found no correlation, and 3 studies described positive and 2 studies reported negative associations between medication adherence and HRQOL. The results indicate that an improved HRQOL may be a trigger for non-adherence in patients with COPD. CONCLUSIONS: The relationship between medication adherence and HRQOL may be dual. The effect of medication adherence on HRQOL might be a consequence of the effectiveness of therapy and the negative effects (ie, side effects, daily life limitation of therapy, social stigma) that it can generate. HRQOL might also influence the patterns of patients' drug use, as an increased HRQOL might trigger non-adherence. The dynamics between adherence and HRQOL might differ over time, as the negative effects of medication non-adherence might become dominant in the long term.