Background: According to CDC, Obesity in the US affects 100.1 million (41.9%) adults and 14.7 million (19.7%) children and accounts for approximately $147 billion in annual healthcare costs. As per WHO, obesity has tripled in the world between 1975 and 2016. As obesity is increasing at such a profound pace, so is the use of medications for its management. Thus, It is equally important to know the safety profile of these medications, specifically in the form of post-marketing surveillance from realworld data. Cardiovascular (CV) comorbidities are very commonly associated with obesity because of common risk factors. Unfortunately, limited data is available describing the CV safety profile of these anti-obesity medications, hence we attempted to study this. Methods: We queried the Food and Drug Administration (FDA)'s Adverse Event Reporting System (FAERS) database for various different Adverse Events (AE) of Orlistat, Phenteramine-topiramate, Tirzepatide, and semaglutide along with CV AEs including hypertension, arrhythmia, heart failure, ventricular hypertrophy, and so forth. The data on these AEs were collected, analyzed, and compared for all four drugs using descriptive statistics. Results: We found a total of 915 CV AEs reported combining all the Anti-obesity medications mentioned above. Out of all the AEs reported for Tirzepatide, there were only 0.71% (35) AEs related to the CV system, compared to Phenteramine-Topiramate, which had the highest CV AEs reported as 3.3% (111) out of all AEs reported. CV AEs associated with Orlistat and Semaglutide were found to be 1.51% (446) and 1.99% (323) respectively. Conclusions: Tirzepatide has 4.5 times less associated CV AEs as compared to phentermine-Topiramate and about 2 times less associated CV AEs compared to Semaglutide and Orlistat. Hence, Tirzepatide followed by Orlistat can be relatively safer to use for patients with Cardiovascular comorbidities as compared to other medications used for the management of Obesity among patients with CV comorbidities. Our study will help clinicians to select appropriate anti-obesity medication among patients with certain comorbidities. With, the increasing use of anti-obesity medications, further clinical studies are required to establish the CV and overall safety profile of these medications especially among patients with certain comorbidities.