Since 2000, resurgence in bed bugs has occurred in the U.S. Reports of infestations of homes, hospitals, hotels, and offices have been described. On September 1, 2011, complaints of itching and bites among workers in an office were reported to the Tennessee Department of Health. A retrospective cohort study and environmental assessments were performed in response to the complaints. Canines certified to detect live bed bugs were used to inspect the office and arthropod samples were collected. Of 76 office workers, 61 (80%) were interviewed; 39 (64%) met the case definition. Pruritic maculopapular lesions were consistent with arthropod bites. One collected arthropod sample was identified as a bed bug by three entomologists. Exposures associated with symptoms included working in a cubicle in which a canine identified bed bugs (risk ratio [RR]: 1.8; 95% confidence interval [CI]: 1.3–3.6), and self-reported seasonal allergies (RR: 1.6, 95% CI: 1.0–2.4). Bed bugs represent a reemerging and challenging environmental problem with clinical, psychological, and financial impacts.