OBJECTIVE: To determine whether introducing a rapid test for meticillin resistant Staphylococcus aureus (MRSA) screening leads to a reduction in MRSA acquisition on hospital general wards. DESIGN: Cluster randomised crossover trial. SETTING: Medical, surgical, elderly care, and oncology wards of a London teaching hospital on two sites. MAIN OUTCOME MEASURE: MRSA acquisition rate (proportion of patients negative for MRSA who became MRSA positive). PARTICIPANTS: All patients admitted to the study wards who were MRSA negative on admission and screened for MRSA on discharge. INTERVENTION: Rapid polymerase chain reaction based screening test for MRSA compared with conventional culture. RESULTS: Of 9608 patients admitted to study wards, 8374 met entry criteria and 6888 had full data (82.3%); 3335 in the control arm and 3553 in the rapid test arm. The overall MRSA carriage rate on admission was 6.7%. Rapid tests led to a reduction in median reporting time from admission, from 46 to 22 hours (P<0.001). Rapid testing also reduced the number of inappropriate pre-emptive isolation days between the control and intervention arms (399 v 277, P<0.001). This was not seen in other measurements of resource use. MRSA was acquired by 108 (3.2%) patients in the control arm and 99 (2.8%) in the intervention arm. When predefined confounding factors were taken into account the adjusted odds ratio was 0.91 (95% confidence interval 0.61 to 1.234). Rates of MRSA transmission, wound infection, and bacteraemia were not statistically different between the two arms. CONCLUSION: A rapid test for MRSA led to the quick receipt of results and had an impact on bed usage. No evidence was found of a significant reduction in MRSA acquisition and on these data it is unlikely that the increased costs of rapid tests can be justified compared with alternative control measures against MRSA. TRIAL REGISTRATION: Clinical controlled trials ISRCTN75590122 [controlled-trials.com].