BACKGROUND Effective hand hygiene has long been recognised as an important way to reduce the transmission of bacterial and viral pathogens in healthcare settings. However, many studies have shown that adherence to hand hygiene remains low, and improvement efforts have often not delivered sustainable results. The Children's Hospital at Westmead is the largest tertiary paediatric hospital in Sydney, Australia. The hospital participated in a state-wide 'Clean hands save lives' campaign which was initiated in 2006. INTERVENTION Strong leadership, good stakeholder engagement, readily accessible alcohol-based hand rub at the point of patient care, a multifaceted education programme, monitoring of staff, adherence to recommended hand hygiene practices and contemporaneous feedback of performance data have significantly improved and maintained compliance with hand hygiene. RESULTS Hand hygiene compliance has increased from 23% in 2006 to 87% in 2011 (p<0.001). Sustained improvement in compliance with hand hygiene has been evident in the last 4 years. A decline in a set of hospital-acquired infections (including rotavirus, multiresistant organism transmission, and nosocomial bacteraemia) has also been noted as hand hygiene rates have improved. Monthly usage of alcohol-based hand rub has increased from 16 litres/1000 bed days to 51 litres/1000 bed days during this same period. CONCLUSION This project has delivered sustained improvement in hand hygiene compliance by establishing a framework of multimodal evidence-based strategies.