OBJECTIVES: Latin America has a high prevalence of Helicobacter pylori infection and associated diseases, including gastric cancer. Antibiotic therapy can eradicate the bacterial infection and decrease associated morbidity and mortality. To tailor recommendations for optimal treatments, we summarized published literature and calculated region- and country-specific prevalences of antibiotic resistance. METHODS: Searches of PubMed and regional databases for observational studies evaluating H. pylori antibiotic resistance yielded a total of 59 independent studies (56 in adults, 2 in children, and 1 in both groups) published up to October 2013 regarding H. pylori isolates collected between 1988 and 2011. Study-specific prevalences of primary resistance to commonly prescribed antibiotics were summarized using random-effects models. Between-study heterogeneity was assessed by meta-regression. As a sensitivity analysis, we extended our research to studies of patients with prior H. pylori-eradication therapy. RESULTS: Summary prevalences of antimicrobial primary resistance among adults varied by antibiotic, including 12% for clarithromycin (n=35 studies), 53% for metronidazole (n=34), 4% for amoxicillin (n=28), 6% for tetracycline (n=20), 3% for furazolidone (n=6), 15% for fluoroquinolones (n=5), and 8% for dual clarithromycin and metronidazole (n=10). Resistance prevalence varied significantly by country, but not by year of sample collection. Analyses including studies of patients with prior therapy yielded similar estimates. Pediatric reports were too few to be summarized by meta-analysis. CONCLUSIONS: Resistance to first-line anti-H. pylori antibiotics is high in Latin American populations. In some countries, the empirical use of clarithromycin without susceptibility testing may not be appropriate. These findings stress the need for appropriate surveillance programs, improved antimicrobial regulations, and increased public awareness.