In 1976, the national swine influenza vaccination program in the United States was suspended because of an increased risk of Guillain-Barré syndrome. Subsequent studies of seasonal influenza vaccine have given conflicting results. The authors used the self-controlled case series method to investigate the relation of Guillain-Barré syndrome with influenza vaccine and influenzalike illness using cases recorded in the General Practice Research Database from 1990 to 2005 in the United Kingdom. The relative incidence of Guillain-Barré syndrome within 90 days of vaccination was 0.76 (95% confidence interval: 0.41, 1.40). In contrast, the relative incidence of Guillain-Barré syndrome within 90 days of an influenzalike illness was 7.35 (95% confidence interval: 4.36, 12.38), with the greatest relative incidence (16.64, 95% confidence interval: 9.37, 29.54) within 30 days. The relative incidence was similar (0.89, 95% confidence interval: 0.42, 1.89) when the analysis was restricted to a subset of validated cases. The authors found no evidence of an increased risk of Guillain-Barré syndrome after seasonal influenza vaccine. The finding of a greatly increased risk after influenzalike illness is consistent with anecdotal reports of a preceding respiratory illness in Guillain-Barré syndrome and has important implications for the risk/benefit assessment that would be carried out should pandemic vaccines be deployed in the future.