Silver sulfadiazine is commonly used in the treatment of partial-thickness burns, but it sometimes forms pseudo-eschar and delays wound healing. Polyhexanide/betaine gel, a new wound cleansing and moisturizing product, has some advantages in removing biofilm and promotes wound healing. This study was designed to compare clinical efficacy of polyhexanide/betaine gel with silver sulfadiazine in partial-thickness burn treatment. From September 2013 to May 2015, 46 adult patients with partial-thickness burn ≥10% total body surface area that were admitted to the Burn Unit of Siriraj Hospital within 48 hours after injury were randomly allocated into 2 groups. One group was treated with polyhexanide/betaine gel, and the other group was treated with silver sulfadiazine. Both groups received daily dressing changes and the same standard care given to patients with burns in this center. Healing times in the polyhexanide/betaine gel group and silver sulfadiazine group were 17.8 ± 2.2 days and 18.8 ± 2.1 days, respectively (P value .13). There were no significant differences in healing times, infection rates, bacterial colonization rates, and treatment cost in both groups. The pain score of the polyhexanide/betaine gel group was significantly less than the silver sulfadiazine group at 4 to 9 days after treatment (P < .001). The satisfactory assessment result of the polyhexanide/betaine gel group was better than that in the silver sulfadiazine group. These data indicate the need for adequately designed studies to elicit the full potential of polyhexanide gel as a wound dressing for partial-thickness burn wounds.