Objective: We present a post-hoc analysis of the safety and efficacy of duloxetine, a selective serotonin/ norepinephrine reuptake inhibitor, for treatment of diabetic peripheral neuropathic pain (DPNP) in older patients. Methods: Data from three double-blind, placebo-controlled trials in adult patients with DPNP were pooled and stratified by age ( < 65, ≥65 years). Patients were randomized to duloxetine (DLX) 60 mg once-daily, 60 mg twice-daily, or placebo for 12 weeks, followed by a 52-week extension phase (re-randomization to routine care or DLX 120 mg/day). Intent-totreat analyses were used for safety and efficacy assessment. Results: In the acute phase, overall TEAE rates did not differ significantly by age. A greater percentage of older patients discontinued due to TEAEs (P < 0.001), regardless of treatment group. Duloxetine improved weekly mean 24-hour average pain scores versus placebo in both age groups (P < 0.01). In the extension phase, a significant therapy-by-age interaction (P < 0.05) was observed in overall TEAE rate; with routine care, 86.6% of older patients had ≥1 TEAE versus 74.6% of younger patients. Conclusions: Although TEAEs more frequently lead to discontinuation in older patients, duloxetine was well tolerated and efficacious for treatment of DPNP regardless of age. These data suggest duloxetine may be beneficial for treatment of DPNP in patients ≥65.