Background Loss-of-function (null) mutations within the filaggrin (FLG) gene are a strong risk factor for atopic dermatitis (AD). We hypothesized that the absence or reduction of the filaggrin protein could compromise skin barrier and increase patients' susceptibility to recurrent skin infection. Objectives To investigate the association between FLG-null mutations and the risk of recurrent skin infection among a series of patients with AD in Singapore. Methods This study included 228 Singaporean Chinese patients with AD with at least 1 year of follow-up at the time of recruitment between January 2008 and December 2009 at the National Skin Centre in Singapore. Each patient had their medical records reviewed for history of skin infection in the preceding year and was genotyped for 22 FLG-null mutations. Results Compared with those without the FLG-null mutations, patients with AD who had FLG mutation(s) had approximately a seven times increased risk of more than four episodes of skin infection requiring antibiotics in the past year (odds ratio 6·74; 95% confidence interval 2·29-19·79). This risk was much greater in those with mild or moderate disease, and was present in both users and nonusers of oral steroids. Conclusion This study highlights a novel association between FLG-null mutations and an increased susceptibility to recurrent bacterial skin infection among patients with AD. © 2011 British Association of Dermatologists.