PROBLEM: Bloodstream infections associated with catheters were the most common nosocomial infections in one paediatric intensive care unit in 1994-7, with rates well above the national average. DESIGN: Clinical data were collected prospectively to assess the rates of infection from 1994 onwards. The high rates in 1994-7 led to the stepwise introduction of interventions over a five year period. At quarterly intervals, prospective data continued to be collected during this period and an additional three year follow-up period. SETTING: A 292 bed tertiary care children's hospital. KEY MEASURES FOR IMPROVEMENT: We aimed to reduce our infection rates to below the national mean rates for similar units by 2000 (a 25% reduction). STRATEGIES FOR CHANGE: A stepwise introduction of interventions designed to reduce infection rates, including maximal barrier precautions, transition to antibiotic impregnated central venous catheters, annual handwashing campaigns, and changing the skin disinfectant from povidone-iodine to chlorhexidine. Effects of change Significant decreases in rates of infection occurred over the intervention period. These were sustained over the three year follow-up. Annual rates decreased from 9.7/1000 days with a central venous catheter in 1997 to 3.0/1000 days in 2005, which translates to a relative risk reduction of 75% (95% confidence interval 35% to 126%), an absolute risk reduction of 6% (2% to 10%), and a number needed to treat of 16 (10 to 35). LESSONS LEARNT: A stepwise introduction of interventions leading to a greater than threefold reduction in nosocomial infections can be implemented successfully. This requires a multidisciplinary team, support from hospital leadership, ongoing data collection, shared data interpretation, and introduction of evidence based interventions.