The efficacy of imidacloprid 10 %/moxidectin 2.5 % (Advocate®, Advantage® Multi, Bayer) against experimental Dirofilaria (D.) repens infection in dogs was evaluated in a blinded, negative controlled randomised laboratory efficacy study. On SD (study day) 0, eight dogs received a spot-on treatment at a dose of 10 mg imidacloprid and 2.5 mg moxidectin per kg body weight. Another 8 dogs were left untreated. On SD 28 each dog was infected with approximately 75 infective D. repens larvae. Blood samples were collected every 4 weeks after treatment. A modified Knott test was conducted to detect mf (microfilaria). PCR analysis was performed with mf-positive blood samples. On SDs 245 and 246, all dogs were euthanised for detection of D. repens worms. Blood samples of all treated dogs were negative for mf at all sampling days. Blood samples of control dogs were positive for mf in 5 out of 8 control dogs. Individual mf counts ranged from 7 to 2800 mf/ml. In mf-positive blood samples, only D. repens was identified by PCR analysis. During necropsy D. repens worms could be detected in eight untreated control dogs (range: 3–21 worms per dog), whereas no worm could be detected in any of the treated dogs. These results indicate a 100 % preventive efficiency of a single spot-on treatment of imidacloprid 10 %/moxidectin 2.5 % in dogs against experimental infection with D. repens (L3 larvae). The product was well tolerated in all study animals, no treatment related adverse reactions were observed throughout the study.