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Background: The association of body mass index (BMI) and waist circumference (WC) with risk of Guillain-Barré syndrome (GBS) has been inconsistent in previous studies. Methods: We examined the associations of BMI and WC in relation to risk of GBS among 252,980 participants from the Nurses' Health Study (NHS), NHS-II, and the Health Professional Follow-up Study (HPFS). BMI and WC were assessed by self-reported questionnaire, and GBS cases were self-reported. Results: We documented 328 incident GBS cases during a total of 5,422,788 person years of follow-up. Compared to participants with BMI<25kg/m2, the multivariate pooled hazard ratio (HR) of GBS was 1.34 (95% CI: 1.04, 1.73) for overweight participants (25kg/m2≤BMI<30 kg/m2), and 1.68 (95% CI: 1.21, 2.35) for obese participants (BMI≥30 kg/m2) (P for trend = 0.001). Compared to participants with normal WC (<35 inches for women and <40 inches for men), the HR of GBS was 1.55 (95% CI: 1.10, 2.18) for participants with high WC (≥35 inches for women, and ≥40 inches for men). The positive associations of BMI and WC with risk of GBS were attenuated to null after mutually adjusting for BMI and WC. Joint analysis showed that the HR was 1.84 (95% CI: 1.27, 2.66) for participants with high WC and BMI≥25 kg/m2 in comparison to participants with normal WC and BMI<25kg/m2. Conclusion: These data from large cohorts showed that higher BMI and WC jointly were associated with higher risk of GBS. Our study highlighted the importance of maintaining a normal body weight and waist circumference in prevention of GBS. [ABSTRACT FROM AUTHOR]