The authors conducted a population-based case-control study to investigate whether clinically observed chickenpox, linked with a level of intensity for clinical expression, increases the risk of multiple sclerosis (MS) in childhood. The cases were MS patients whose disease onset occurred between 1994 and 2003, before age 16 years, in France. Each case was matched for age, sex, and geographic origin with as many as 12 controls randomly selected from the general population. Information about clinically observed chickenpox in cases and controls before the index date regarding onset of MS was collected with a standardized questionnaire and was checked against health certificates. Conditional logistic regression was used to estimate the odds ratio for an association between MS and chickenpox. The 137 MS cases were matched with 1,061 controls. Clinically observed chickenpox had occurred in 76.6% of the cases and 84.9% of their matched controls. The adjusted odds ratio of MS onset associated with chickenpox occurrence was 0.58 (95% confidence interval: 0.36, 0.92). The authors concluded that clinically observed chickenpox was associated with a lower risk of childhood-onset MS in a French population.