Postherpetic neuralgia (PHN) is the most common complication of varicella zoster virus (VZV) reactivation and a cause of considerable physical and psychosocial morbidity. No known treatment effectively prevents the development of PHN in patients with VZV reactivation. In this study, our objective was to evaluate the efficacy of premedication with gabapentin for reducing the risk of PHN in patients with diabetic and nondiabetic neuropathy. We retrospectively searched the electronic health records of patients with diabetic and nondiabetic neuropathy treated with gabapentin at Mayo Clinic before diagnosis of VZV reactivation. In total, PHN developed in 7 patients with diabetic neuropathy receiving gabapentin (n=62 [11.3%]) compared with 26 not receiving premedication with gabapentin (n=50 [52.0%]) (odds ratio, 0.12; 95% CI, 0.05-0.31; P<.001); PHN developed in 11 patients with nondiabetic neuropathy receiving gabapentin (n=109 [10.1%]) compared with 108 not receiving premedication with gabapentin (n=217 [49.8%]) (odds ratio, 0.11; 95% CI, 0.06-0.22; P<.001). In this cohort of patients with neuropathy, gabapentin administration before the onset of VZV reactivation significantly reduced the risk of PHN.