Background Reduced appetite is a common clinical sign in dogs. This study evaluated the effectiveness and safety of capromorelin oral solution, (ENTYCE®, Aratana Therapeutics, Leawood, KS) a new drug that is a ghrelin receptor agonist, for stimulation of appetite in dogs with reduced appetite. Hypothesis/Objectives Capromorelin will increase appetite, as measured by the owner's evaluation, over 4 days. An additional objective was to evaluate the safety of capromorelin at the labeled dose. Animals A total of 244 client‐owned dogs reported by owners to be inappetent for at least 2 days were enrolled, with 177 cases in the effectiveness analysis. Methods In this prospective, randomized, masked, placebo‐controlled study, dogs were treated daily with capromorelin (3 mg/kg) oral solution (n = 121) or placebo oral solution (n = 56). Owners completed an evaluation of appetite at days 0 and 3 ± 1. Success was defined as improvement in appetite at day 3. Safety was evaluated by physical examination, clinical pathology, and monitoring adverse events and owner observations. Results Capromorelin treatment improved appetite compared to placebo (68.6% and 44.6% treatment successes with 95% CI 59.7, 76.3 and 32.2, 57.8, respectively, P = .008). Mean body weight in capromorelin‐treated dogs increased compared to placebo‐treated dogs (1.8% with 95% CI 1.3, 2.3, and 0.1% with 95% CI 0.9, 1.1, respectively, P < .001). Adverse reactions occurring in >5% of either group were diarrhea and vomiting. Conclusions and Clinical Importance Capromorelin oral solution is an effective treatment for stimulation of appetite in dogs and represents the first ghrelin receptor agonist shown to be effective for this indication.