Aim: To compare the efficacy and safety of topical Mupimet (2% mupirocin in a novel Cogen-S base) against mupirocin alone in the management of skin ulcers. Methods: We conducted a randomised controlled trial (RCT) with patients suffering from skin ulcers of Wagner grading 1 or 2 for over 4 weeks. Both the medications were applied topically twice daily for 12 weeks. Ulcer area, wound size and wound infection score were assessed on a five-point scale. During this study period, treatment-emergent adverse reactions were not observed either by the investigators or by the patients. The results were expressed as mean± standard deviation values to imply the wound size of the foot ulcer from the baseline to the week 12. Results: We recruited 50 patients, with 21 patients treated with mupirocin 2% and 24 patients treated with Mupimet ointment (five were lost to follow-up). We observed that the ulcer area was significantly reduced in the test groups (2% mupirocin in novel Cogen-S base) at 10 weeks, whereas the control group demonstrated a decrease in the wound size of over a period of 12 weeks. Statisical comparison using a t-test between two groups was conducted and showed statistical significance between the two groups in the study. When compared with the control value after 12 weeks, the test value is highly significant (p≤0.05 control and p≤0.05 test). Conclusion: The wound healing effect of topical Mupimet (in Cogen-S base) with the antimicrobial effect of mupirocin toward the overall management of skin ulcers. The acceleration of wound healing is higher in combined form than mupirocin alone.