In veterinary practice pain alleviation plays a part in managing lameness. The aim of this randomized and placebo-controlled clinical study was to evaluate the effect of a single administration of ketoprofen on locomotion characteristics and weight distribution in cattle with foot (located up to and including the fetlock; n = 31) and (proximal to the fetlock; n = 10) pathologies. Cattle were randomly allocated to either the ketoprofen (group K; intravenous 3 mg/kg of body weight; n = 21) or an equivalent volume of isotonic sterile saline solution (group P; n = 20). Two accelerometers (400 Hz; kinematic outcome = stance phase duration; kinetic outcome = foot load and toe-off), a 4-scale weighing platform (weight distribution and SD of the weight) and a subjective locomotion score were measured before (baseline) and after 1 h and 18 h of treatment. All variables were expressed as differences across contralateral limbs, and the measurements at 1 h and 18 h were compared to the baseline. A repeated measures ANOVA was used to determine the differences between groups K and P. A logistic regression model with a binary outcome (0 = no improvement and 1 = improvement of the differences across the contralateral limbs over time) was calculated. Mean (± SD) of locomotion scores at baseline were not significantly different (P = 0.102) in group K (3.10 ± 0.80) as compared to group P (3.48 ± 0.64). Cattle of group K showed significantly lower differences across contralateral limbs at 1 h as compared to group P for the relative stance phase and the weight distribution. Only the treatment (P versus K) remained a significant factor in the model for relative stance phase (odds ratio (OR) = 6.5; 95% CI = 1.38-30.68) and weight distribution (OR = 6.36; 95% CI = 1.30-31.07). The effects of ketoprofen were evident in improving the differences across contralateral limbs-both for stance phase during walking and weight bearing during standing-after 1 h but not after 18 h of administration.