Drug interactions are significant considerations for intradermal testing (IDT). Trazodone (TRZ) is an anxiolytic and selective histaminergic (H1 ) antagonist with no interaction in human prick tests; however, interaction in canine IDT is unknown. Trazodone will not adversely affect intradermal histamine reactions in dogs. Fourteen nonanxious, nonatopic, healthy client-owned dogs were enrolled in this randomised, blinded, cross-over study. Dogs were randomised to receive low-dose TRZ (4 mg/kg) (Teva Pharmaceuticals), high-dose TRZ (8 mg/kg) or no TRZ per os two hours before intravenous sedation with dexmedetomidine (5 mcg/kg) (Dexdomitor; Zoetis). Intradermal testing was performed with five quadrupling dilutions of histamine (1:100,000 to 1:25,600,000 w/v; Greer) and 0.9% saline (Hospira), observing a minimum two weeks washout period between treatments. Two observers, who were blinded to treatment and the identity of the injections, evaluated each test using previously established subjective and objective methods. The mean wheal diameter of histamine 1:1,600,000 w/v was significantly smaller with low-dose TRZ (4 mg/kg) compared to the control group (p = 0.048; repeated measures ANOVA with post hoc Tukey's test). For all other histamine dilutions and saline, mean wheal diameter was not significantly different among groups. There were no significant differences in the subjective scores of all histamine dilutions and saline (p > 0.05; Friedman test). A single oral dose of TRZ does not adversely affect intradermal histamine reactions in dogs.