International variability in infarct size following acute anterior ST-elevation myocardial infarction without shock treated with primary percutaneous coronary intervention (PCI) has been little studied. Patients enrolled in the Counterpulsation to Reduce Infarct Size pre‐PCI for Acute Myocardial Infarction international randomized trial were analyzed according to their region of enrollment: United States (US) (n = 60), Europe/Australia (EU/AU) (n = 104), or India (n = 123). Cardiac magnetic resonance imaging was performed 3–5 days after PCI to assess infarct size, expressed as percentage of left ventricular mass, and analyzed by an imaging core laboratory. The relation between infarct size and region was modelled using multivariable linear regression adjusting for time from symptom onset to first hospital contact, myocardial infarction severity, and baseline characteristics. Infarct size was 36.4% of left ventricular mass in US patients (95% confidence interval [CI] 31.5 to 41.4), 36.5% (95% CI 32.6 to 40.4) in EU/AU patients, and 44.7% (95% CI 41.1 to 48.2) in patients from India (p = 0.01). In multiplicity-adjusted regression analysis, mean infarct size in patients from India was higher than in US patients (mean difference of 8.3%; 95% CI 0.7 to 15.8; p = 0.03), and EU/AU patients (mean difference of 8.2%; 95% CI 1.6 to 14.8; p = 0.01). There was no significance difference in infarct size between patients from the EU/AU and the US (mean difference of 0.1%; 95% CI −7.5 to 7.4; p = 0.99). ln conclusion, in patients with anterior ST-elevation myocardial infarction without cardiogenic shock treated with primary PCI, infarct size was larger in India compared to the United States and EU/AU, even after adjustment for performance metrics, including time to treatment, and other potential confounders. Future studies are needed to better elucidate this discrepancy.