Derquantel (DQL), a semi-synthetic member of a novel anthelmintic class, the spiroindoles, in combination with abamectin (ABA) [as the combination product STARTECT(®)] is a new entry for the treatment and control of parasites in sheep. The 19 studies reported herein were conducted in Australia, New Zealand, South Africa and the United Kingdom to demonstrate the efficacy of derquantel-abamectin (DQL-ABA) against a broad spectrum of gastrointestinal and respiratory nematodes of sheep, and to support registration of the combination product. Eleven studies were conducted using natural or experimental parasite infections with unknown or unconfirmed resistance, while eight studies utilised isolates/strains with confirmed or well characterised resistance to one or more currently available anthelmintics, including macrocyclic lactones. All studies included DQL-ABA and negative control groups, and in selected studies one or more reference anthelmintic groups were included. In all studies the commercial formulation of DQL-ABA was administered orally at 2mg/kg DQL and 0.2mg/kg ABA; placebo was administered in the same volume as DQL-ABA; and reference anthelmintics were administered as per label recommendations, except in one instance where levamisole was administered at twice the label dose. Infection, necropsy, worm collection and worm counting procedures were performed using standard techniques. Efficacy was calculated based on the percentage reduction in geometric mean worm count relative to negative control for each nematode species and lifecycle stage targeted. Twenty-two isolates/strains used in the eight studies targeting resistant worms had proven resistance: three to one anthelmintic class, eleven to two classes and eight to three or more classes; of these resistant strains, 16 demonstrated resistance to a macrocyclic lactone anthelmintic. Regardless of resistance status in the 19 studies, DQL-ABA controlled a broad range of economically important gastrointestinal and respiratory nematode parasites of sheep, as follows: ≥ 98.9% efficacy against Haemonchus contortus (adult and L4); Teladorsagia circumcincta (adult, L4 and hypobiotic L4); Teladorsagia trifurcata (L4); Trichostrongylus axei (adult and L4); Trichostrongylus colubriformis (adult and L4); Trichostrongylus falculatus (adult); Trichostrongylus rugatus (adult); Trichostrongylus vitrinus (adult and L4); Cooperia curticei (adult and L4); Cooperia oncophora (adult and L4); Nematodirus spathiger (adult); Nematodirus battus (adult); Nematodirus spp. (hypobiotic L4); Strongyloides papillosus (adult); Strongyloides spp. (L4); Chabertia ovina (adult); Oesophagostomum venulosum (adult); Dictyocaulus filaria (adult); and Protostrongylus rufescens (adult); ≥ 97.0% efficacy against Trichuris ovis (adult); and ≥ 95.9% efficacy against T. trifurcata (adult). Derquantel-abamectin is a highly effective combination anthelmintic, which will provide an important new tool for controlling helminths of sheep when used in conjunction with sustainable drenching practices.