Background: Our goal was to determine whether immunization is associated with the incidence of Guillain-Barré syndrome (GBS). Methods: We analyzed data for all patients registered with 253 general practices in the United Kingdom General Practice Research Database from 1992 to 2000, with a mean of 1.8 million registered patients. We identified new occurrences of GBS and estimated age- and sex-specific and age-standardized incidence rates. We then determined whether the date of diagnosis was made within 42 days of any immunization and estimated the relative risk of diagnosis following immunization after adjusting for age and sex. Results: There were 228 incident cases of GBS, including 107 women and 121 men. The age-standardized incidence rate per 100 000 person-years was 1.22 (95% confidence interval [CI], 0.98-1.46) in women and 1.45 (95% CI, 1.19-1.72) in men. Age-specific incidence rates per 100 000 person-years were highest in men aged 65 to 74 years (3.86; 95% CI, 2.50-5.70) and women aged 75 to 84 years (2.54; 95% CI, 1.39-4.27). There were 7 cases (3.1%) in which the onset occurred within 42 days of any immunization; 3 of the 7 cases occurred after influenza immunization. There were 221 cases (97.0%) that were not associated with immunization. The adjusted relative risk during the 42 days after immunization was 1.03 (95% CI, 0.48-2.18; P = .94). Conclusions: There is either minimal or no risk of GBS associated with routine immunization practice in the United Kingdom. Obtaining a precise estimate of any potential risk associated with an individual vaccine would require a study with more GBS cases.