The ability of the plant-derived compound nootkatone to control nymphs of the blacklegged tick, Ixodes scapularis Say, was evaluated at lawn perimeter plots at homes in Lyme disease endemic areas of Connecticut. Three formulations of nootkatone ranging from 0.05 to 0.84% (0.06–1.03 g AI/m2) were applied by a hydraulic sprayer from 2008 to 2010. In 2008, the 0.84% emulsifiable nootkatone formulation provided 100% control of I. scapularis through week 1, but declined to 49 and 0% by 2 and 3 wk posttreatment, respectively. A combination of 0.05% nootkatone and entomopathogenic fungus, Metarhizium brunneum Petch F52, resulted in 50% control for the first week posttreatment and no control in subsequent weeks. The 0.84% emulsifiable nootkatone formulation was phytotoxic, although no damage was observed with the 0.05% formulation with Metarhizium. Residual analysis of nootkatone collected on filter paper disks showed that ≥95% of the emulsified nootkatone for both formulations was lost within 7 d after application. A lignin-encapsulated nootkatone formulation (0.56 and 0.46% in 2009 and 2010, respectively) provided 100% control of I. scapularis for 8 wk in 2009 and, in 2010, 67% control at ≈1 wk posttreatment with respect to the pretreatment counts, although there was no difference in tick abundance posttreatment. A 0.60% Maillard-reaction encapsulated nootkatone formulation in 2010 provided a similar level of control (62%). Nootkatone in the lignin and Maillard formulations were more persistent than the emulsifiable formulation. Little or no phytotoxicity was observed with the encapsulated formulations. Encapsulating nootkatone reduced phytotoxicity and appeared to reduce environmental loss. While nootkatone can provide effective tick control, further work is needed to refine formulations to address phytotoxicity, yet provide sufficient material to control ticks.