An interventional longitudinal study was conducted in 52 French dairy farms endemically affected by digital dermatitis (DD) to concurrently estimate the effect of treatment and management practices on DD incidence. Farms were allocated in one of four treatment regimens and followed 7 times every 4 weeks. Cox frailty survival models including time-varying covariates were used to estimate the effect of potential risk factors and treatment practices on the time until the first case of DD. These models identified that high initial DD prevalence strongly increased the hazard for DD occurrence, as well as absence of hoof-trimming, and poor leg cleanliness. “Prim’Holstein” and high-productive cows were found to be most likely to develop DD. Collective treatments tended to decrease the hazard for DD occurrence only when applied at least every fortnight, compared to only individual topical treatments. These results confirm the multi-factorial character of DD and provide useful data to design prevention programmes