Introduction Despite many therapeutic options, painful diabetic neuropathy is still a common and challenging complication of diabetes mellitus and is often resistant to treatment with current modalities.

Methods In this randomized, single-blind clinical trial we compared the efficacy of parenteral vitamin B₁₂ and nortriptyline, for symptomatic improvement of pain, paresthesia, burning, freezing, stabbing and electrical sensation.. Changes in nerve conduction parameters of amplitude, duration and latency were also compared.

Results One hundred patients (50 in each group) completed the study. After treatment, the pain score based on a visual analogue scale decreased 3.66 units in the vitamin B₁₂ group and 0.84 units in the nortriptyline group (P <0.001). Similarly, the paresthesia score decreased 2.98 units versus 1.06 units (P <0.001). The decrements of tingling sensation were 3.48 units versus 1.02 units (P <0.001). Changes in vibration, position, pinprick and nerve conduction parameters were not significant in two groups.

Conclusion In conclusion, vitamin B₁₂ is more effective than nortriptyline for the treatment of symptomatic painful diabetic neuropathy.