Despite recommendations in most countries for giving inactivated influenza vaccine to people with asthma, only a minority currently receive it. One reason for low vaccine coverage has been concern that vaccination may induce exacerbations of asthma. In this randomized trial, 291 patients between 18 and 65 years of age received either an inactivated influenza vaccine followed 14 days later by a saline placebo or placebo followed by the vaccine. Each patient received 1 dose of vaccine and 1 dose of placebo. The percentage of patients reporting at least one asthma exacerbation within 14 days after injection was similar following vaccine or placebo (28.3% and 25.5%, respectively). The combined exacerbation rate during the first 14-day interval was higher (31.5%) than that during the second 14-day interval (22.4%, P = 0.0135), indicating that the occurrence of exacerbations was not likely to be related to the sequence of injections. The percentages of individuals with solicited systemic symptoms were 56.6% and 44.8% after vaccine or placebo injection, respectively. We conclude that influenza vaccination did not increase the incidence of asthma exacerbations compared to placebo in this study and the vaccine was well tolerated. The results thus support annual influenza vaccination in patients with asthma.