In recent years the rates of Clostridium difficile infection (CDI) have increased worldwide with several large outbreaks occurring within the UK. New guidance from the UK Department of Health describes measures to investigate periods of increased incidence (PII) of CDI which include informing staff, ribotyping isolates, enhanced cleaning, audits and monitoring of antibiotic prescribing. This study aimed to determine whether a standardised set of measures could be used to control the incidence of CDI within an acute hospital setting over an 18 month period. During the study period a total of 102 PII involving 439 patients were investigated. The number of PII per month ranged from 14 in February 2008 to one in June 2009. From January 2008 to September 2008, ribotyping of patient isolates was only carried out on PII involving more than 10 patients, but from October 2008 it was carried out on all PII. During the period October 2008 to June 2009, 28 PII were investigated on 21 different wards, with seven wards having two PII. Ribotyping of the isolates confirmed nine (32%) of these PII to be outbreaks, with three being due to ribotype 027, two ribotype 078 and the others distinct ribotypes. Use of a set of standardised interventions has resulted in a decrease in the incidence of PII and a reduction in the number of patients involved. By taking early action with a set of standardised measures the incidence of hospital-acquired CDI can be reduced.