Trazodone hydrochloride is a tetracyclic antidepressant commonly used in human, gaining popularity in feline patients as a pre-appointment anxiolytic and sedative medication. However, the oral administration route in cats poses difficulties for owners and limits practicality. This study evaluated the efficacy and safety of transdermal trazodone in cats. At the first visit, the cat stress score (CSS), global sedation score (GSS), behavioral response score (BRS), and owner-assessed overall experience score (OES) were used to observe and record the behavior during transportation and examination. Thereafter, each cat was given 150 mg of transdermal trazodone before the second visit. The respiratory rate, heart rate, pulse rate, systolic blood pressure, blood test, adverse effects, and response time were compared between the two visits. Thirteen cats were enrolled in this study. Transdermal trazodone significantly lowered CSS of outward trip (P = 0.005) and return trip (P = 0.005) (Wilcoxon signed-rank test). No significant differences were observed in CSS and GSS during the examination. Moreover, the BRS was significantly low (P = 0.018), but the significance varied depending on the examination procedure and behavior. The OES questionnaire showed a significant reduction in stress during the outward trip (P = 0.002), return trip (P = 0.005), and examination (P = 0.003) (all Wilcoxin signed ranks test). Physiologic parameters and laboratory values were not significantly affected, and the adverse effects were few and mild. In conclusion, transdermal trazodone was well tolerated at a single dose of 150 mg/cat. It can reduce stress and anxiety before a veterinary visit, resulting in a better patient-owner experience.