The objective of this study was to determine the effect of an injection of 10% butaphosphan and cyanocobalamin (Catosal, Bayer, Shawnee Mission, KS) on the day of calving and 1 d later on the prevalence of subclinical ketosis in dairy cattle in the early postpartum period. Cows from 4 herds (n=1,122) were randomized to receive either 25. mL of 10% butaphosphan and cyanocobalamin or 25. mL of sterile water subcutaneously on both days. Each milliliter of Catosal contained 0.05. mg of cyanocobalamin and 100. mg of butaphosphan, which provided 17.3. mg of P in the form of [1-(butylamino)-1-methylethyl]-phosphonic acid. Serum was sampled for β-hydroxybutyrate (BHBA) concentration at calving (pretreatment) and again between 3 and 10 d in milk. A subset of samples from mature cows was also evaluated for serum Ca and P concentrations. When cows from all age groups were included in the analysis, there was no difference between the median serum BHBA concentrations of cows in the 2 treatment groups, and no difference in the proportion of hyperketonemic cows (serum BHBA ≥1,200μmol/L) during the first week postpartum. When the analysis was restricted to mature cows (lactation ≥3), both the median BHBA concentration and the proportion of hyperketonemic cows were significantly lower in the treatment group than in the placebo group. Serum Ca and P concentrations did not differ between treatment groups. Our results suggest that injection of butaphosphan and cyanocobalamin on the day of calving and 1 d later may decrease the prevalence of subclinical ketosis during the week after calving in mature dairy cows, but not in first- and second-lactation animals.