A recombinant fowlpox vaccine with an H5 hemagglutinin gene insert protected chickens against clinical signs and death following challenge by nine different highly pathogenic H5 avian influenza viruses. The challenge viruses had 87.3 to 100% deduced hemagglutinin amino acid sequence similarity with the recombinant vaccine, and represented diversely geographic and spatial backgrounds; i.e. isolated from four different continents over a 38 year period. The recombinant vaccine reduced detectable infection rates and shedding titers by some challenge viruses. There was a significant positive correlation in hemagglutinin sequence similarity between challenge viruses and vaccine, and the ability to reduce titers of challenge virus isolated from the oropharynx (r(s)=0.783, P=0.009), but there was no similar correlation for reducing cloacal virus titers (r(s)=-0.100, P=0.78). This recombinant fowlpox-H5 avian influenza hemagglutinin vaccine can provide protection against a variety of different highly pathogenic H5 avian influenza viruses and frequent optimizing of the hemagglutinin insert to overcome genetic drift in the vaccine may not be necessary to provide adequate field protection.