Trigeminal neuralgia (TN) is the most common type of neuralgia affecting facial region and is considered to be one of the most painful conditions. Treatment is often unsatisfactory. Newer treatment modalities are therefore being tried. Duloxetine is FDA approved drug for painful diabetic neuropathy and has been used in painful symptoms of depression as well. Safety and efficacy of duloxetine was evaluated in patients with trigeminal neuralgia; another chronically painful condition, in an open label manner. A total of 15 patients who fulfilled the diagnostic criteria of International Headache Society for Trigeminal Neuralgia were administered duloxetine 40 mg daily. The efficacy of the drug was evaluated by face scale and Likert's numerical scale. Statistically significant pain relief was reported in 9 out of 15 patients of trigeminal neuralgia. The pain relief was reported as early as in one week and was maintained for 16 weeks. The drug was well tolerated and side-effects reported were mild and reversible. No adverse drug reaction requiring hospitalisation or drug discontinuation was reported in the present study. Duloxetine showed statistically significant pain relief in trigeminal neuralgia. Double-blind, placebo-controlled studies are needed to confirm findings at a large scale.