The treatment of hyperketonemia [HK, blood β-hydroxybutyrate (BHBA) ≥ 1.2 mmol/L] with oral propylene glycol has proven benefits. Parenteral administration of glucocorticoids has been suggested as an adjunctive therapy, however it has not been assessed in a randomized field trial setting. The objective of this research was to evaluate the effect on cure rate of a one-time intramuscular injection of dexamethasone as an adjunctive therapy for hyperketonemia. A randomized control trial was conducted from May to August 2014 on 4 dairy farms in New York State. Cows were tested from 3 to 16 d in milk, once weekly, for blood BHBA using the Precision Xtra device. All cows testing positive for HK were randomly assigned to receive a single intramuscular injection of 20 mg dexamethasone (DX) or an equivalent volume of sterile saline placebo (PB). Both groups received 4 d of oral propylene glycol therapy. Cure risk was determined by blood BHBA obtained the week following enrollment. A multivariable multi-level logistic regression model was constructed for the outcome of being ketotic at first follow-up. Herd was controlled as a random effect. A total of 498 cows were enrolled, 248 treated with DX and 250 receiving PB. At first follow-up, 250 individuals (50.2%) remained HK. Of those, 131 (52.4%) were from the DX group and 115 (46.0%) from the PB group (P = 0.26). Lactation number and BHBA at enrollment modified the effect of treatment. The odds of recovering were higher in first lactation animals treated with DX compared with PB treated first-lactation animals (OR: 3.59 CI: 1.29–10.03). Cows enrolled with BHBA at 1.2 and 1.4 mmol/L and treated with DX had odds of recovering 2–3 times higher (OR: 3.09, CI: 1.65–5.75, OR: 2.31, CI: 1.39–3.83, respectively) than those treated with the PB. There is no significant association between treatment and cure risk at higher BHBA at enrollment. Adding DX to HK treatment protocols was beneficial for cows in first lactation or had a blood BHBA at enrollment of 1.2 or 1.4 mmol/L.