In June 2002, the Pediatric Infectious Diseases Group (GPIP) reported to the French Institute for Public Health Surveillance an increase in severe cases of chickenpox requiring hospitalization. The majority of severe cases were linked to a secondary skin infection. A study aimed at better understanding the risk factors (specifically the use of talcum powder) for the development of secondary skin infections in children with chickenpox was conducted in September 2004 to guide preventive measures. A case-control study was conducted in hospitals within the pediatric departments of mainland France participating in the Chickenpox Observatory and volunteering to take part in the study. The data collection period spanned from April 2004 to September 2006. The study population consisted of children with chickenpox presenting at the hospital (hospitalization, emergency department visit, or outpatient visit). A case was defined as a child with chickenpox and a skin superinfection. A control was defined as a child with chickenpox without a skin superinfection. Cases and controls were identified by clinicians: each subject meeting the case definition was included, followed by the next subject meeting the control definition. Variables collected in part by telephone from parents included sociodemographic and economic characteristics, disease severity, anthropometric measurements, hygiene practices, and treatments taken prior to arrival at the hospital. Data were analyzed using a logistic regression model. A total of 234 patients (109 cases and 125 controls) were included. The distribution by sex and age was comparable in both groups. The variables significantly associated with the occurrence of cutaneous superinfection at the 5% threshold in multivariate analysis were the use of powder (Nisapulvol® and other types of talc) (OR=3.5 [1.5–8.1]), the use of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR=3.7 [1.8–7.8]), the presence of high fever at admission (OR=4.3 [2.2–8.2]), and the mother’s occupational status (OR=3.0 [1.4–6.8] for children whose mothers were in the “managerial” socioeconomic category compared to those whose mothers belonged to other occupational categories. No hygiene practices were associated with the occurrence of secondary infection. The results of this study confirm the hypothesis that the use of powders is a risk factor for the occurrence of a secondary skin infection in children with chickenpox. The use of NSAIDs is associated with the occurrence of cutaneous superinfection, but a causal link cannot be definitively established by this study. These results help identify practices associated with a risk of cutaneous superinfection and support the current recommendations of the Afssaps not to use talcum powder or NSAIDs in the treatment of chickenpox (R.A.)