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Abstract Management of the Colorado potato beetle (Leptinotarsa decemlineata) is reliant on conventional insecticides that can negatively affect non-target arthropods. Calantha™ (active ingredient: ledprona) is a sprayable double-stranded RNA biopesticide specific forL decemlineataproteasome subunit beta 5 gene that triggers the RNA-interference pathway and is designed to have limited non-target effects. To test this hypothesis, we conducted two years of field trials in Idaho, Wisconsin, and Maine comparing arthropod responses to different insecticide regimes, with and without Calantha, targeting the Colorado potato beetle. Comparisons of arthropod abundance among treatments showed no evidence of effects of Calantha on non-target arthropods, including beneficials (predators, parasitoids), “neutrals” (i.e., non-pests), and other beetle species. Conventional insecticides generally showed more non-target effects, and responses were always stronger for arthropods from vacuum samples than pitfall samples. Insecticide programs featuring Calantha, especially in rotation with other biorational products, may reduce pests while preserving beneficial arthropods and contribute to biological control of arthropod pests in potato fields.