Objective. To describe the characteristics and interventions to control a large epidemiological Influenza A Outbreak. Methods. During the months of February to April 2006, a large outbreak of Influenza A was detected, which affected Health Care Workers and hospitalized patients in a large teaching Hospital in Guatemala City. Interventions to interrupt transmission were implemented and included barrier methods (N95 masks, respiratory isolation measures, etc.) and enhanced hand hygiene, vaccination of healthy Health Care Workers (HCW), restrictions for patient visits. Results. From February to April 2006, 59 hospitalized patients diagnosed with Influenza A. 19 AIDS patients (mortality: 71%) and 5/40 (12.5%) in other diseases: cancer (3), severe cardiac failure (1) and severe malnutrition (1). The attack rate at day 20 in doctors and medical students was 21% while in other HCW it was 10.5%. Within 3 weeks of the beginning of the plan, deaths were stopped and no more cases in HCW were detected after 3 additional weeks. Conclusion. A rapid, comprehensive plan for the control of nosocomial epidemic Influenza A outbreaks is essential to limit severe morbidity and mortality in hospitals who attend large immunocompromised populations, including AIDS patients. HCW regular vaccinations programs are mandatory.