Introduction: Fabry disease, a lysosomal storage disease consisting of an alpha-galactosidase-A deficiency, is associated with multi-organ disease including the liver, kidneys, and heart. New enzyme replacement and gene therapies have emerged in recent years to treat Fabry disease. Hypothesis: We aim to study temporal trends and cardiovascular outcomes in hospitalized patients with Fabry disease. Methods: Using the National Inpatient Sample (NIS) database we collected major adverse cardiovascular events (MACE) including arrhythmias, acute myocardial injury, stroke, cardiac arrest, and heart failure that occurred each year from 2017-2019. Appropriate ICD-10 codes were used for data collection. Proportions were calculated and adjusted odds ratios OR were determined using the Charlson Comorbidity Index. Results: Overall, there was an increase in total hospitalizations in patients with Fabry disease from 2017 to 2019. Fabry disease was associated with increased risk of MACE (OR=2.88, CI 1.99-3.68, P<0.000) when compared with patients without Fabry disease. There was a significantly higher proportion of MACE in Fabry disease when compared to the general population from 2017-2019 (P-trend <0.000). Secondary outcomes showed a increased risk of arrhythmias (OR=4.89, CI 3.22-7.08, P<0.000) and heart failure (OR=4.34, CI 2.90-6.50, P<0.000), but no significantly increased risk of acute myocardial injury (OR=3.11, CI 0.96-4.62, P=0.07) or stroke (OR=1.79, CI 0.76-2.41, P=0.11). Conclusions: Fabry disease is associated with worse inpatient cardiovascular outcomes when compared to patients without Fabry disease. Tissue injury from infiltrative deposits may cause subsequent myocardial fibrosis and conduction diseases, leading to heart failure and conduction diseases, respectively.