Present study was undertaken to compare the effectiveness of venlafaxine, bupropion with amitriptyline in diabetic neuropathic pain. This was an open, parallel, prospective and randomized type study conducted at the outpatient departments of medicine and neurology of Era’s Lucknow Medical College & Hospital, Lucknow and Chhatrapati Shahuji Maharaj Medical University, Lucknow, respectively, to compare the effects of venlafaxine, bupropion and amitriptyline in patients suffering from diabetic neuropathic pain. Present study gives following conclusions: 1). Pain scores improvement (decrease) was highest in amitriptyline followed by venlafaxine followed by bupropion. 2). QOL scores improvement (decrease) was highest in venlafaxine followed by bupropion and least in amitriptyline. 3). NCVs (m/s) improvement (increase) was highest in amitriptyline in all the studied nerves except RCPN. 4). In RCPN, the NCV (m/s) improvement (increase) was highest in venlafaxine followed by bupropion followed by amitriptyline.