Separation anxiety in dogs is a problematic behavior characterized by anxiety that occurs exclusively in the owner's absence or virtual absence, resulting in owner complaints of destructiveness, excessive vocalization, and elimination in the home. The consequences of separation anxiety may include that the owners surrender their dog to a shelter, or even have the dog euthanized. Adrenergic alpha-2 agonists have been shown to be effective in alleviating acute canine fear-based behavior problems at subsedative doses. In this study, the objective was to assess the efficacy of tasipimidine, a novel orally administered adrenergic alpha-2 agonist, in alleviating acute anxiety associated with owner departure in dogs. Twelve clinically healthy privately-owned dogs with a history of separation anxiety were enrolled in a double-blind, placebo-controlled, crossover clinical field study consisting of three 4-day treatment periods in randomized order each followed by a 3-day washout. In each treatment period a different treatment was administered. The three treatments were: placebo, tasipidimine 10ug/kg and tasipidimine 30 ug/kg, all prepared as an oral solution using the same base. At each of the 4-day treatment period study treatment was administered once daily one hour before owner´s departure. Effects of treatment on signs of separation anxiety were assessed by the owner using video recordings. Owner departure related acute anxiety severity score, dog's alertness, usability of the product and adverse events were recorded. Overall, the results showed a statistically significant treatment effect favoring tasipimidine (P= 0.001). When the doses were separately compared to placebo, the dog owners rated the effect of the study treatment more often positively after administering tasipimidine 30 µg/kg compared to placebo (OR 5.40; 95% CI 1.15-25.2; P = 0.032). A statistically significant reduction with the 30 µg/kg dose was seen in destructive/rearranging behavior (P = 0.006) and vocalization (P = 0.036). Most of the dogs were scored to be fully responsive at all time points (66.7%) and able to stand up and walk normally (91.7%), and none of the dogs was scored to be unresponsive or unable to walk. No serious adverse events were reported. The majority of the owners found the product very easy (75.0%) or easy (15.7%) to use. This was a small, cross-over study with one target to select the clinically most suitable dose. Tasipimidine should be further studied in a larger parallel group study to further evaluate its effect as a treatment option for dogs suffering from separation anxiety.