Lameness is one of the most significant endemic disease problems facing the dairy industry. Claw horn lesions (principally sole hemorrhage, sole ulcer, and white line disease) are some of the most prevalent conditions. Despite the fact that thousands of animals are treated for these conditions every year, experimental evidence is limited on the most effective treatment protocols. A randomized, positively controlled clinical trial was conducted to test the recovery of newly lame cows with claw horn lesions. Animals on 5 farms were locomotion scored every 2. wk. Cows were eligible for recruitment if they had 2 nonlame scores followed by a lame score and had a claw horn lesion on a single claw of a single foot. Following a therapeutic trim, enrolled cows were randomly allocated to 1 of 4 treatments: treatment 1-no further treatment (positive control; TRM), treatment 2-trim plus a block on the sound claw (TB), treatment 3-trim plus a 3-d course of the nonsteroidal anti-inflammatory drug (NSAID) ketoprofen (TN), treatment 4-trim plus a block plus ketoprofen (TBN). The primary outcome measure was locomotion score 35. d after treatment, by an observer blind to treatment group. Descriptive statistics suggested that treatment groups were balanced at the time of enrollment, that is, randomization was successful. Based on a sound locomotion score (score 0) 35. d after treatment, the number of cures was 11 of 45 (24.4%) for TRM, 14 of 39 (35.9%) for TB, 12 of 42 (28.6%) for TN, and 23 of 41 (56.1%) for TBN. The difference between TBN and TRM was significant. To test for confounding imbalances between treatment groups, logistic regression models were built with 2 outcomes, either sound (score 0) or nonlame (score 0 or 1) 35. d after treatment. Compared with TRM, animals that received TBN were significantly more likely to cure to a sound outcome. Farm, treatment season, lesion diagnosis, limb affected, treatment operator, and stage of lactation were included in the final models. Our work suggests that lameness cure is maximized with NSAID treatment in addition to the common practices of therapeutic trimming and elevation of the diseased claw using a block when cows are newly and predominantly mildly lame.