ST-elevation myocardial infarction (STEMI) systems of care have reduced inter-hospital transfer times and facilitated timely reperfusion goals. Helicopters may be an option when land transportation is not feasible; however, the safety of air transport in patients with acute coronary syndrome (ACS) is a factor to consider. The aim of this study was to evaluate the safety of helicopter transport for patients with ACS. Prospective, observational, and descriptive study including patients diagnosed with ACS within the STEMI network of a metropolitan city transferred by helicopter to a large cardiovascular center to undergo percutaneous coronary intervention. The primary outcome of the study was the incidence of air-travel-related complications defined as IV dislodgement, hypoxia, arrhythmia, angina, anxiety, bleeding, and hypothermia. Secondary outcomes included the individual components of the primary outcome. A total of 106 patients were included in the study; the mean age was 54 years and 84.9% were male. The most frequent diagnosis was STEMI after successful fibrinolysis (51.8%), followed by STEMI with failed fibrinolysis (23.7%) and non-reperfused STEMI (9.4%). Five patients (4.7%) developed at least one complication: IV dislodgement (1.8%) and hypoxemia (1.8%) in two patients and an episode of angina during flight (0.9%). A flight altitude of > 10,000 ft was not associated with complications. The results of this study suggest that helicopter transportation is safe in patients undergoing acute coronary syndrome, despite the altitude of a metropolitan area.