ObjectiveTo determine the likely rate of patient randomisation and to facilitate sample size calculation for a full-scale phase III trial of varicella zoster immunoglobulin (VZIG) and aciclovir as postexposure prophylaxis against chickenpox in children with cancer.DesignMulticentre pilot randomised controlled trial of VZIG and oral aciclovir.SettingEngland, UK.PatientsChildren under 16 years of age with a diagnosis of cancer: currently or within 6 months of receiving cancer treatment and with negative varicella zoster virus (VZV) serostatus at diagnosis or within the last 3 months.InterventionsStudy participants who have a significant VZV exposure were randomised to receive PEP in the form of VZIG or aciclovir after the exposure.Main outcome measuresNumber of patients registered and randomised within 12 months of the trial opening to recruitment and incidence of breakthrough varicella.ResultsThe study opened in six sites over a 13-month period. 482 patients were screened for eligibility, 32 patients were registered and 3 patients were randomised following VZV exposure. All three were randomised to receive aciclovir and there were no cases of breakthrough varicella.ConclusionsGiven the limited recruitment to the PEPtalk2 pilot, it is unlikely that the necessary sample size would be achievable using this strategy in a full-scale trial. The study identified factors that could be used to modify the design of a definitive trial but other options for defining the best means to protect such children against VZV should be explored.Trial registration numberISRCTN48257441, EudraCT number: 2013-001332-22, sponsor: University of Birmingham.