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The purpose of this study was to concurrently estimate the effect of different digital dermatitis (DD) treatment regimens and herd management practices on the occurrence of a new DD lesion. A controlled clinical trial was conducted and involved 4678 dairy cows from 52 French dairy farms where DD was endemic. Farms were allocated by minimisation to one of 4 treatment regimens, varying through the mode (footbath or collective spraying) and the frequency of application (2 days every 4 weeks or fortnightly). They were visited 7 times every 4 weeks by 14 trained investigators. Frailty Cox proportional hazards models were used to estimate the relative effect of potential risk factors and treatment practices on the time until the first occurrence of a DD lesion. At herd level, high initial DD prevalence strongly increased the risk for DD occurrence (HR=1.93, CI 1.23-3.04), as well as absence of hoof-trimming (HR=1.75, CI 1.36-2.27) and poor leg cleanliness (HR=2.44, CI 1.80-3.31). At animal level, Holstein breed (HR=1.92, CI 1.35-3.57) and high-productive cows (HR=1.26, CI 1.01-1.56) were identified to be at higher risk for DD compared to Normande breed and low-productive cows, respectively. Compared to individual topical antibiotic treatments alone, collective treatments tended to decrease the risk of DD occurrence only when applied over 2 days at least every fortnight (HR range=0.64-0.73)., (Copyright © 2013 Elsevier B.V. All rights reserved.)