OBJECTIVES: Dronedarone is a non-iodinated benzofuran derivative approved by FDA in July 2009. It is used for the treatment of abnormal heart rhythm in patients with a history of atrial fibrillation or atrial flutter. The recent evidence suggests there is a potential risk of serious cardiovascular adverse events associated with the use of dronedarone, especially among patients with permanent atrial fibrillation. The objective is to assess the association between use of dronedarone and the risk of serious cardiovascular adverse events and other health outcomes. METHODS: A literature search of peer-reviewed publications relevant to the study was performed using PubMed® from 1996 to 2013. Eight clinical trials with a total of 10,800 patients enrolled were identified for this study.  A meta-analysis of randomized controlled trials comparing patients with or without dronedarone was conducted. The dronedarone group included patients who took dronedarone, and patients who took placebo (7 studies) or amiodarone (1 study) were considered as the control group. Outcomes included all-cause mortality, cardiovascular mortality and heart failure exacerbation. Review Manager 5.2 was used for data analysis. RESULTS: Compared to the control group, the use of dronedarone did not significantly increase the risks of all-cause mortality (Risk Ratio [RR], 1.27; 95% Confidence interval [CI], 0.80 to 2.02), cardiovascular mortality (RR, 1.31; 95% CI, 0.53 to 3.24) and heart failure exacerbations (RR, 1.19; 95% CI, 0.88 to 1.62). However, after conducting the sensitivity analysis which excluded the ATHENA study (the FDA approval of dronedarone was based on this trial), we found dronedarone was statistically significant in increasing the risk of all-cause mortality (RR, 1.70; CI, 1.13 to 2.56), cardiovascular mortality (RR, 2.13; 95% CI, 1.10 to 4.15) and heart failure exacerbations (RR, 1.42; 95% CI, 1.07 to 1.89).  CONCLUSIONS: The healthcare professionals should prescribe dronedarone cautiously for patients with cardiovascular risk factors.