This study investigated the potential factors linked to healthcare-associated infection (HCAI) rates in acute National Health Service hospitals, analysing mandatory surveillance data with existing data available to the Healthcare Commission, and supplemented by a bespoke questionnaire. A questionnaire was developed to cover important elements related to the management and control of HCAI. Additional data were collated from other sources. Infection outcomes comprised the mandatory surveillance data, for both meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia and Clostridium difficile-associated diarrhoea (CDAD). The response rate was 90%. A lower MRSA rate was linked to hand hygiene and isolation and a lower rate of CDAD to cleanliness, good antimicrobial prescribing practices and surveillance of infections. Lower rates of both organisms were related to strategic planned interventions, such as the inclusion of infection control in the staff development programme. However, certain interventions, for example increased levels of training, were related to a higher infection rate. These findings for MRSA and CDAD are supported by evidence from the infection control literature. We have found relationships between interventions and higher infection rates that are counterintuitive and that may represent examples of what we call 'reactive practice' to higher rates of infection. Whilst it is interesting to hypothesise that these interventions may be swift and simple to introduce and may not be sustained compared to more strategic and planned interventions linked to lower infection rates, they most probably simply represent the beginning of a culture change and embedding of infection control practice.