BackgroundScreening men for prostate cancer using prostate-specific antigen (PSA) testing remains controversial. We aimed to estimate the likely budgetary impact on secondary care in England and Wales to inform screening decision makers.MethodsThe Cluster randomised triAl of PSA testing for Prostate cancer study (CAP) compared a single invitation to men aged 50–69 for a PSA test with usual care (no screening). Routinely collected hospital care data were obtained for all men in CAP, and NHS reference costs were mapped to each event via Healthcare Resource Group (HRG) codes. Secondary-care costs per man per year were calculated, and cost differences (and population-level estimates) between arms were derived annually for the first five years following randomisation.ResultsIn the first year post-randomisation, secondary-care costs averaged across all men (irrespective of a prostate cancer diagnosis) in the intervention arm (n= 189279) were £44.80 (95% confidence interval: £18.30-£71.30) higher than for men in the control arm (n= 219357). Extrapolated to a population level, the introduction of a single PSA screening invitation could lead to additional secondary care costs of £314 million.ConclusionsIntroducing a single PSA screening test for men aged 50–69 across England and Wales could lead to very high initial secondary-care costs.