Avian influenza (AI) was diagnosed in May 2002 for the first time in Chile and South America. The epidemic was caused by the highly pathogenic AI (HPAI) virus subtype H7N3 that emerged from a low pathogenic virus. The index farm was a broiler breeder, located in San Antonio, V Region, which at the time was a densely populated poultry area. Stamping of 465,000 breeders, in 27 sheds, was immediately conducted. Surveillance activities detected a second outbreak, 1 wk later, at a turkey breeding farm from the same company. The second farm was located 4 km from the index case. Only 25% of the sheds were infected, and 18,500 turkeys were destroyed. In both outbreaks, surveillance zones and across-country control measures were established: prediagnosis quarantine, depopulation, intensive surveillance, movement control, and increased biosecurity. Other measures included cleaning, disinfection, and controlling the farms with sentinels to detect the potential presence of the virus. Zoning procedures were implemented to allow the international trade of poultry products from unaffected areas. Positive serologic results to H5N2 virus also were detected in other poultry farms, but there was no evidence of clinical signs or virus isolation. Epidemiological investigation and laboratory confirmation determined that positive serology was related to a contaminated imported batch of vaccine against inclusion body hepatitis. All actions taken allowed the control of the epidemic, and within 7 mo, Chile was free of AI. Epidemic and control measures that prevented further spread are described in this article, which illustrates the importance of a combination of control measures during and after an outbreak of AI. This study is a good example of how veterinary services need to respond if their country is affected by HPAI.