We studied therapeutic and prophylactic efficacy of new drugs against ectoparasitosis in dogs and cats. New veterinary drugs for dogs and cats were developed with the combined active substances (Imidacloprid, Pyriproxyfen and Moxidectin) in the form of a spot-on solution for external application at the premises of the VNIIP – FSC VIEV. The difference between the drugs is the different content of Moxidectin – the Moxidectin content is 2.5 times higher in the drug for dogs than the drug for cats. The studies were performed on dogs and cats of different sex, age, body weight and breed spontaneously infected with pathogens of acariasis and entomosis in the settings of the Podolsk Experimental Production Base of the VNIIP – FSC VIEV and in a Moscow veterinary clinic in 2021. Experimental and control groups were formed according to the principle of analogues. The diagnosis and drug efficacy were confirmed holistically based on the anamnestic and epizootological data, clinical picture and laboratory research methods (microscopy of scraps taken from the affected areas of the skin, and examination of the coat for fleas, lice, chewing lice and ixodid ticks). Babesiosis (piroplasmosis) was excluded in the dogs. The drugs were used in the experimental group of animals in the dose range of 0.1–0.4 mL per kg of the body weight of the animal according to the Draft Instructions for Use. It was found that the drugs showed high therapeutic and prophylactic efficacy against sarcoptic mange of dogs, notoedric mange of cats, otodectic mange and entomosis of dogs and cats, as well as ixodid ticks attacking animals.