During the last two decades, the common bed bug (Cimex lectularius L.) (Hemiptera: Cimicidae) has resurged to become a common urban pest. Insecticide sprays are commonly used to manage this pest. However, most of the available insecticide sprays registered for bed bugs are not very effective due to insecticide resistance. Bed bugs are considered one of the most difficult urban pests to control. There is strong interest in developing novel, effective insecticide materials to combat widespread bed bug infestations. Isocycloseram is a novel insecticide in the class isoxazoline that shows excellent efficacy and selectivity against invertebrate pests. We evaluated the direct spray and residual efficacy of two 0.1% isocycloseram formulations ina laboratory against four insecticide-resistant field strains of common bed bugs (Cimex lectularius L.) (Hemiptera: Cimicidae) on three surfaces (fabric, vinyl tiles, and unpainted pinewood). Their efficacy was compared with five commercial insecticides including Demand CS (0.03% γ-cyhalothrin), Temprid FX (0.05% imidacloprid and 0.025% β-cyfluthrin), Crossfire (0.4% clothianidin, 0.01% metofluthrin, and 1.0% piperonyl butoxide), Bedlam Plus (0.4% Cyclopropanecarboxylate, 1.0% N-Octyl bicycloheptene dicarboximide, and 0.05% imidacloprid), and PT Phantom II (0.5% chlorfenapyr). Both isocycloseram 45 SC and 400 SC formulations were the most effective among the tested insecticides. The isocycloseram 45 SC formulation caused faster mortality than the 400 SC formulation. Four hours of exposure to 0.025, 0.05, and 0.1% isocycloseram 45 SC residue on porous and non-porous surfaces caused 100% bed bug mortality after 3-4 days. Exposure to 30 d aged 0.1% isocycloseram 45 SC residue for 4 hours still caused 100% mortality, compared to 0-73% mortality by the five commercial insecticides. Isocycloseram is a highly effective compound for controlling resistant C. lectularius populations