The efficacy of two topically applied antibiotics for the treatment of painful ulcerative stage of bovine digital dermatitis (BDD) lesions was compared in a clinical trial conducted on five dairy farms in the Netherlands during the autumn of 2015. A total of 109 cows with an ulcerative (M2) stage of BDD were randomly appointed a treatment with an antibiotic-based spray. One treatment contained thiamphenicol as active ingredient (TAF). The other treatment had oxytetracycline as active ingredient (ENG). The experimental unit for this study was the hind claw with the presence of an ulcerative BDD lesion. On day 0, claws with ulcerative BDD lesions were trimmed, cleaned, photographed and thereafter treated randomly either with TAF or ENG. Cure was defined as the transition of an ulcerative lesion into a non-painful chronic (M4) or into a healed (M0) stage of BDD at day 28 post-treatment. The cure rate at day 28 of M2 BDD lesions treated with TAF was 89 per cent (95 per cent CI 0.78 to 0.94), and for ENG 75 per cent (95 per cent CI 0.67 to 0.86). So the difference in cure rate was 14 per cent (95 per cent CI 0.00 to 0.27), which was statistically significant. The P value in this experiment is very close to 0.05 indicating that the effect is quite small. If a two-sided test would be used, the small significant effect, in this experiment, will disappear. Overall, the significant better curative effect of TAF on BDD M2 lesions was small, compared with ENG.