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Advances in paediatric healthcare are often the result of randomised clinical trials.1,2 Notable examples include trials on vaccines,3 surfactant in preterm infants,4 and oncology.5 Researchers, healthcare providers, and parents acknowledge the importance of research, but effective recruitment into paediatric clinical trials remains a difficult task.6-9 Barriers to participation in paediatric research have been well described in the literature,10-16 but the literature on strategies for recruiting critically ill infants for clinical trials is limited.17-19 The concept of equipoise or the “uncertainty principle” can present challenges to recruitment in randomised controlled trials, especially when the study drug is routinely used in clinical practice.20 The ethical principle is upheld if there is true uncertainty about which trial arm is most likely to benefit the patient.20 Preconceived notions of efficacy on the part of the investigators should be discussed in advance to eliminate the lack of equipoise as a potential barrier to recruitment. The purpose of this report is to describe the key challenges for recruitment, the strategies implemented to address these challenges, and lessons learned from this experience. In the case of neonates with complex congenital cardiac diseases and functionally univentricular hearts, parents are under extreme stress when approached to participate in research, especially if the diagnosis was not made prenatally. Parents are mourning the loss of an expected “healthy child” and adjusting to the new realities of a child who will require multiple surgical and other procedures before 3 years of age. Appropriate practices and strategies of recruitment during this emotional time are key to engaging parents and their medical providers in a conversation about clinical research and securing successful enrolment of infants. In 2001, the Pediatric Heart Network was established by the National Heart, Lung, and Blood Institute, National Institutes of Health to conduct multi-centre clinical research in children with cardiovascular disease.21 After successful recruitment to an observational study22 and a randomised placebo-controlled drug trial in Kawasaki disease,23 the Pediatric Heart Network launched the “Angiotensin-Converting Enzyme Inhibition in Infants with Single Ventricle Trial” or the “Infant Single Ventricle Trial”.24,25 This double-blind, randomised placebo-controlled trial compared the effects of enalapril with placebo on somatic growth in 230 neonates with functionally univentricular hearts. After the “Infant Single Ventricle Trial” began, recruitment was more challenging than in previous studies and enrolment began to lag. Efforts to understand and remediate the problems were further complicated by the launch of the Pediatric Heart Network’s “Single Ventricle Reconstruction Trial”, a randomised surgical trial comparing two types of surgical shunts, in May, 2005,26,27 which recruited shortly after birth a subset of infants eligible for the “Infant Single Ventricle Trial”.