OBJECTIVES: To evaluate and compare changes in healthcare resource utilization and costs associated with the initiation of pregabalin or gabapentin in pDPN patients in a real-world setting. METHODS: A retrospective cohort study utilizing the MarketScan Commercial Claims and Encounters Database (2007-2009). Patients with a new prescription for pregabalin or gabapentin in 2008 (date of the prescription defined as index date) and ≥1 healthcare encounter with an ICD-9 code for diabetic peripheral neuropathy (DPN; 250.6 or 357.2) within 30 days prior to the first prescription for pregabalin or gabapentin were identified and propensity score matched. Both cohorts were continuously enrolled for the 12 month pre- and post-index periods during which health care utilization and costs were assessed. Pre- to post-index changes were compared between pregabalin and gabapentin using a difference-in-difference (DID) approach. RESULTS: 910 pregabalin patients (48.6% female; mean age 63.3±12.1 years) were matched to 910 gabapentin patients (48.8% female; mean age 63.3±12.1 years); other demographic and clinical characteristics were also comparable between cohorts, with the exception of US region. The pre- to post-index DID in resource utilization did not differ between the two cohorts including: number of office visits per patient (P=0.66), number of ER visits (P=0.78), number of inpatient stays (P=0.92), average inpatient length of stay per hospitalization (P=0.79), number of total prescriptions filled (P=0.37). The DID of total healthcare costs per patient were non-significant with pre- to post-index increases of $3,081 in pregabalin patients and $4,683 in gabapentin patients (P=0.50). CONCLUSIONS: Patients with pDPN initiating pregabalin or gabapentin experienced comparable changes in healthcare resource utilization and costs. These results suggest overall cost neutrality between pregabalin and gabapentin.