Background: Adequate pain control, an essential part of cancer care remains a challenge in resource limited countries like Nepal. Early use of morphine for Moderate Cancer Pain (MCP) and not sequential World Health Organization (WHO) analgesic ladder seems reasonable in the setting of limited access to health care. The purpose of this study was to compare efficacy of oral Morphine (MOR) with oral Tramadol (TRM) in control of pain as well as physical wellbeing in patients (pts) with MCP using Edmonton Symptom Assessment Scale (ESAS). Methods: An IRB approved randomized phase II trial was performed in opioid-naive pts with MCP as defined by pain score in Numerical rating score (NRS)of 4-6.Patients were randomized to receive MOR syrup 5 mg 4 hourly or TRM 50 mg four times a day. Titration of dose was done in both groups for 3 days as per standard recommendation for MOR or till maximum recommended daily dose for TRM. MOR was changed to prolonged release form at Day 4.The primary endpoint was number of early responders, defined as pts with at least 20% reduction in pain intensity on NRS on Day 3. Secondary outcome was number of patients with highly meaningful pain reduction, defined as decrease in pain intensity on NRS by ≥ 5 and improvement in physical well-being with ESAS at Day 7. Results: 68 pts consented and were randomized, 34 in each arm. The primary endpoint occurred in 94.1% pts in MOR and 55.9% in TRM (p <0.001). Number of patients with highly meaningful pain reduction was significantly higher in MOR than in TRM (76.5% vs. 32.35%; p<0.001). Improvement in general physical wellbeing as assessed by ESAS was better in morphine group. No difference in adverse effects was noted between the treatment arms. Conclusions: In this study Morphine was superior to Tramadol in the control of pain with statistically significant difference in the primary and secondary endpoints. So, early use of morphine skipping the WHO sequential analgesic ladder for moderate cancer pain seems a higher value option in resource scarce country with limited access to healthcare.