OBJECTIVES: Omalizumab is a monoclonal antibody, indicated for the treatment of severe allergic asthma. In Europe, there have been concerns about the cardiovascular safety of omalizumab. The objective of this study is to analyze the association between omalizumab and arterial thrombotic events (ATE) in spontaneous adverse drug reaction reporting database in the United States. METHODS: Reports of ATE submitted to the US Food and Drug Administration’s Adverse Event Reporting System (AERS) between 2004 and 2011 were retrieved and analyzed by the reporting odds ratio (ROR) data mining algorithm. The ROR of ATE for omalizumab was compared to specific asthma medications and all drugs in the AERS. Values of >1 are considered significant safety signals. Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms were used to retrieve ATE (e.g. stroke, myocardial infarction). RESULTS: A total of 293,783 reports of ATE were retrieved (about 2% of all ADR reports), corresponding to 2,274 asthma drug-event pairs (omalizumab, 222; inhaled corticosteroids (ICS), 131; long-acting beta-agonists (LABA), 102; single-device combination ICS/LABA, 506; inhaled short-acting beta-agonists (SABA), 475; oral SABA, 6; inhaled antimuscarnics (AMC), 477; single-device combination AMC/SABA, 127; xanthines, 50; leukotriene modifiers, 174; and mast cell stabilizers, 4). ROR and 95%CI values for omalizumab compared to other asthma drugs and all drugs in AERS were 2.75 (2.39-316) and 1.09 (0.95-1.24), respectively. Omalizumab ranked the second after ICS in the risk of ATE; followed by AMC, AMC/SABA, and ICS/LABA. CONCLUSIONS: Omalizumab is associated with higher than expected reporting of arterial thrombotic events in asthmatic patients. This hypothesis needs further testing in robust epidemiologic studies.