HIV infection increases the risk of acute myocardial infarction (AMI). However, little is known about its effect on in-hospital outcomes and temporal trends in AMI patients undergoing percutaneous coronary intervention (PCI). We queried AMI patients who underwent PCI from the National Inpatient Sample Database (2003–2015) and stratified into three groups: symptomatic, asymptomatic, and HIV-negative. After 1:2 case-control matching (CCM), logistic regression analysis was conducted to determine how HIV infection affected in-hospital outcomes, and we also evaluatedtheir recent trends from 2003-2015. A total weighted national estimate of 2,191,129 AMI cases included 2,178,995 HIV/AIDS-negative cases, 4,994 asymptomatic HIV cases, and 7,140 symptomatic HIV cases. Symptomatic but not asymptomatic HIV patients endured an over tripled in-hospital mortality (aOR 3.84, 95% CI 2.63-5.62), over two-fold of the acute kidney injury (aOR 1.90, 95% CI 1.42–2.54) and the cardiac shock risk (aOR 1.83, 95% CI 1.24-2.70), a longer length of hospital stay (beta 1.27, 95% CI 1.04-1.51), and had more procedures (beta 1.30, 95% CI 1.16-1.44). These disparities related to symptomatic HIV infection lasted from 2003 to 2015. In AMI patients who underwent PCI procedures, symptomatic HIV infection is associated with higher in-hospital mortality and severe outcomes.