OBJECTIVES: A myriad of pharmacologic agents are developed in attempts to control obesity, including the extension of the antiepileptic topiramate as an antiobesity agent. However, concerns about the safety of such agents are mounting. This study aimed at evaluating the cardiovascular and congenital (CC) safety of marketed antiobesity agents, including topiramate. METHODS: A pharmacovigilance analysis of adverse event reports spontaneously submitted to the US Food and Drug Administration’s Adverse Event Reporting System (AERS) from 2004 to 2011 was conducted. The Proportional Reporting Ratio (PRR) data mining algorithm is used to detect signals of CC adverse events that are reported for orlistat, phentermine, sibutramine, and topiramate. Safety signals are detected for PRR values >2. The values are compared within antiobesity class and to all drugs in AERS. RESULTS: A total of 41,930 adverse event reports for antiobesity agents were submitted to the AERS during the study period. About 4% and 1% of the reports were for cardiovascular and congenital problems, respectively. Compared to all drugs in AERS, antiobesity agents didn’t show higher than expected reporting of cardiovascular events (PRR 0.71, 95%CI 0.68-0.74). However, they showed significant safety signals regarding congenital anomalies (PRR 7.45, 95%CI 6.82-8.0), which were mostly attributed by topiramate. Compared to other antiobesity agents, sibutramine was associated with higher cardiovascular reporting rates (PRR 4.42, 95%CI 4.0-4.85), e.g. cardiac arrhythmias, pulmonary hypertension, hypertension, coronary artery disease, and stroke. Phentermine was associated with valvular heart disease (VHD), pulmonary hypertension, and stroke. Topiramate was associated with congenital anomalies and VHD. CONCLUSIONS: Antiobesity agents should be prescribed with caution to patients with cardiovascular risk factors. Regulatory authorities should define cardiovascular safety surveillance requirements for antiobesity agents at postmarketing stages of product’s lifecycle. An alternative to topiramate should be prescribed to females of childbearing age. Epidemiological studies are warranted to test the generated hypotheses.