BACKGROUND: A significant proportion of the world's population lives with physical disability (PD) requiring healthcare services. Risk factors for cardiovascular disease (CVD) such as hypertension and diabetes are more prevalent among patients with PD. Our study compares outcomes following acute myocardial infarction (AMI) between patients with preexisting PD and those without, using the National Inpatient Sample (NIS). METHODS AND RESULTS: We analyzed all adult inpatients having a diagnosis of AMI from 2015 to 2018. The main outcome measured was in-hospital all-cause mortality. Of 2,674,524 patients admitted with AMI, 5% had PD. Patients in the PD group were found to have higher mortality (aOR 1.13, CI 1.1-1.15 p < 0.001), with the musculoskeletal group showing the highest mortality. Patients with PD received lower rates of percutaneous coronary intervention (aOR 0.65, CI 0.64-0.66, <0.001), compared to the non-PD group, with the musculoskeletal group having the lowest rates of intervention. CONCLUSION: A diagnosis of PD was independently associated with significantly increased mortality following AMI. The prognostic impact of disability correlates with the nature of the disability, with musculoskeletal disability being associated with the worst mortality outcomes. Finally, patients with any type of PD are less likely to be offered invasive cardiac management following their AMI.