BACKGROUND: Bovine tuberculosis (TB) has re-emerged as a major problem for British cattle farmers. Failure to control the infection has been linked to transmission from European badgers; badger culling has therefore formed a component of British TB control policy since 1973. OBJECTIVES AND DESIGN: To investigate the impact of repeated widespread badger culling on cattle TB, the Randomised Badger Culling Trial compared TB incidence in cattle herds in and around ten culling areas (each 100 km2) with those in and around ten matched unculled areas. RESULTS: Overall, cattle TB incidence was 23.2% lower (95% confidence interval (CI) 12.4-32.7% lower) inside culled areas, but 24.5% (95% CI 0.6% lower-56.0% higher) higher on land <or=2 km outside, relative to matched unculled areas. Inside the culling area boundary the beneficial effect of culling tended to increase with distance from the boundary (p=0.085) and to increase on successive annual culls (p=0.064). In adjoining areas, the detrimental effect tended to diminish on successive annual culls (p=0.17). On the basis of such linear trends, the estimated net effect per annum for culling areas similar to those in the trial was detrimental between the first and second culls, but beneficial after the fourth and later culls, for the range of analyses performed. CONCLUSIONS: Careful consideration is needed to determine in what settings systematic repeated culling might be reliably predicted to be beneficial, and in these cases whether the benefits of such culling warrant the costs involved.