A simulation model including two hosts (horses and donkeys) and one vector (Culicoides imicola) for African horse sickness in Spain is extended to consider vaccination strategies. If hosts were protected prior to virus introduction, elimination of simulated epidemics was related nonlinearly to the fraction protected. Protecting donkeys as well as horses increased the effectiveness of vaccination. Prevention of 50% of epidemics required 75% coverage of horses and donkeys or 90% coverage of horses only. Protection after the introduction of the virus was rarely successful in preventing outbreaks. If horses alone were protected, the number of donkeys was the most significant factor determining the level of protection needed to prevent an epidemic. If both hosts were protected, the abundance of other hosts for vector blood meals was the most significant factor. These results suggest that prophylactic vaccination of both horses and donkeys with high coverage is necessary to prevent outbreaks of African horse sickness in Spain.