BACKGROUND: Antibiotic resistance is a growing problem worldwide, with differences in regional resistance patterns driven by variance in antibiotic stewardship. Hospitals along the United States-Mexico border increasingly identify resistance, raising concern for transfer of drug-resistant organisms across the border. METHODS: This retrospective review evaluated trauma admissions between March 2011 and August 2015. Patients were included if cultures were obtained during the first 3 days of hospitalization to limit analysis of hospital-acquired bacteria. A matched Mexico and US cohort subanalysis was later compared to eliminate bias in time from injury to culture. RESULTS: Among 115 Mexico and 1,149 US patients, Mexico patients were younger (mean 44.3 vs 60.4 years), had a higher median injury severity score (21 vs 10), and longer hospital durations of stay (mean 11.6 vs 5.5 days). These differences resolved in the matched analysis. Infections were more common in Mexico than US patients in the matched cohort, and resistant infections including resistant gram-negative infections were more common in Mexico patients in both the matched and overall cohorts. The only resistant organism identified in matched US patients was methicillin-resistant Staphylococcus aureus. Extended-spectrum ß-lactamase Klebsiella was found only in patients from Mexico. Additional risk factors for resistance in the matched cohorts included injury in Mexico, ≥2 days from injury to admission, and tracheostomy placement in Mexico. CONCLUSION: Antibiotic resistance is more common in patients initially treated in Mexico healthcare facilities than those treated exclusively in the United States and may require alternative empiric treatment. Global initiatives to improve antibiotic stewardship will be critical to limit the continued rise in drug-resistant infections.