Introduction: Antiepileptics and antidepressant medications are known for managing neuropathic pain. We aim to compare the effects of pregabalin with low-dose amitriptyline and gabapentin with low-dose amitriptyline in managing neuropathic pain in cancer patients undergoing palliative care. Materials and Methods: We conducted our study on 160 cancer patients who were having neuropathic pain and were undergoing palliative care treatment in our institute. It was a hospital-based, randomized, tertiary cancer center-based observational study. After taking approval from the institutional ethics committee and taking written informed consent from patients, the patients were divided into two groups and the effect of medicines on incidence of neuropathic pain was observed; the incidence of burning sensation and the incidence of adverse effects of medications were also analyzed. Statistical analysis was done using paired t-test and SPSS version 20 software. Results: The onset of relief in pain was earlier in the pregabalin group as compared to the gabapentin group. There was more reduction in a burning sensation in the pregabalin group as compared to the gabapentin group. The incidence of headaches was the same in both groups. Nausea and vomiting were more in the pregabalin group but the overall difference in adverse effects was not statistically significant (P > 0.05) Conclusions: In the management of neuropathic pain in cancer patients who are undergoing palliative care, a combination of pregabalin with amitriptyline was found to be more effective in pain relief than gabapentin with amitriptyline.