Aelurostrongylus abstrusus is the most important respiratory nematode of domestic cats. Effective control options are crucial to protect health and welfare of cats and to reduce the spread of aelurostrongylosis in both enzootic and free regions. The present study evaluated the efficacy of a spot-on formulation containing 280 mg/ml fluralaner and 14 mg/ml moxidectin (Bravecto® Plus, MSD) in the prevention of aelurostrongylosis in cats under field conditions. One hundred and fifty-two cats from Italy, Hungary and Bulgaria, were randomly divided in two groups, one treated with Bravecto® Plus on Study Days (SDs) 0 and 84 (74 cats, IVP Group) and one left untreated (78 cats, control group). Faecal samples were collected from all animals on SDs 42 ± 4, 84, 126 ± 4 and 168 ± 4 and subjected to the Baermann’s technique and species-specific PCR for A. abstrusus. Each cat was subjected to a clinical examination on SDs 0, 84 and 168 ± 4 to check health condition and possible adverse events. The results of the faecal analysis were statistically analyzed for treatment group differences in the percentage of cats negative to the Baermann’s test and PCR and percentage of reduction of fecal larvae counts as the primary and secondary efficacy criteria, respectively. The percentage of negative cats was higher in the IVP group compared to the control group and the percentage of reduction of fecal larvae counts in the IVP group compared to the control group was 100%. These results show that two administrations of Bravecto Plus® spot-on 12 weeks apart were safe and effective in the prevention of aelurostrongylosis for a period of almost 6 months.