OBJECTIVES:    To evaluate the effects on direct and indirect costs of initiating pregabalin or duloxetine in employees diagnosed with painful diabetic peripheral neuropathy (pDPN). METHODS:  Employees (18-64 years old) with a diagnosis of DPN and at least one claim for a pDPN-related pain medication were identified using the Thomson Reuters MarketScan® Commercial Claims and Encounters Research Database (2005-2008).  Patients were continuously enrolled in the 6-month pre- and 6-month post-initiation periods. To control for selection bias, propensity scored matched pregabalin and duloxetine new starts were evaluated. Key study outcomes including imputed medically-related work loss, prescription and healthcare utilization, and associated expenditures were analyzed using bivariate statistics and multivariate models in a difference-in-difference approach. RESULTS:   A total of 946 employees with pDPN (473 per group) were identified.  In the pre-index period, there were no statistically significant differences between groups in age (mean 54.0 ± 5.6 pregabalin and 53.3 ± 7.5 duloxetine), gender (females 52% pregabalin, 48% duloxetine), geographic distribution, insurance plan types, comorbidities, medication use, health care resource utilization or healthcare expenditures.  The average number of prescriptions in the 6-month post-index period was 2.9 ± 1.9 for pregabalin and 3.1 ± 2.1 for duloxetine.  There were no significant differences between treatment groups for pre-to-post changes in opioid utilization (marginal effect 1.3 percentage points fewer pregabalin opioid patients, p=0.328) as well as the number of pDPN-related pain medications (marginal effect 0.108 more medications for pregabalin, p=0.506).  The adjusted marginal effects for pre-to-post changes in all-cause health care expenditures ($154 greater increase for pregabalin patients, p=0.895), pDPN-attributable expenditures ($145 greater increase for pregabalin patients, p=0.359) and indirect costs ($458 relative decrease for pregabalin patients, p=0.324) were not statistically significant.   CONCLUSIONS:   There were no significant pre-to-post differences between pregabalin and duloxetine treatment groups in opioid use, DPN-related pain medication use, pDPN-attributable, all-cause and indirect expenditures.