OBJECTIVES: Adverse drug events (ADE) have a considerable adverse impact on human health, and have been associated with increased healthcare costs. Several studies addressed the economic burden of drug-related morbidity, but, to date, no attempt has been made to estimate the average costs of ADE. The aim of this systematic review is to estimate costs related with ADE. METHODS: MEDLINE and Cochrane Library were searched from 1995 up to 2015. Experimental and observational studies, economic evaluations and systematic reviews were included. Methodological quality of selected studies was assessed by Cochrane Collaboration tool for experimental and observational studies, Evers Checklist for economic evaluations and PRISMA guideline for systematic reviews. Studies were classified according to the setting analyzed in “Ambulatory”, and “Hospital”. Costs were classified as “Direct” and “Indirect”. Data were analyzed using descriptive statistics. RESULTS: Forty-one (82%) observational studies, 5 (10%) economic evaluations and 4 (18%) systematic reviews were included. Economic evaluations were the type of study assessed with the highest methodological quality score. The mean study duration was 29 months [2 weeks–127 months]. Most of the studies assessed the median costs of any ADE (n=30; 60%). Thirty-three (66%) studies evaluated any therapeutic group. Thirty-two (64%) studies estimated costs of ADE in “Hospital” setting. “Direct medical costs” were the most frequently type of costs evaluated (n=26; 84%). The unit of measure and the way how the costs were estimated varied widely across the studies. CONCLUSIONS: Several studies have investigated the costs related with ADE. However, due to the wide variety of study methodology, settings analyzed, and type and unit of measurement of costs evaluated, no conclusions can be drawn. Further work is warranted to standardize this type of study in order to properly estimate the economic burden of ADE.