Background: Nurses working in a northern Australia Radiation Therapy Unit advise all patients undergoing radiation therapy to use a readily available nonprescription moisturizing cream to minimize the severity of radiation skin reactions. However, patients report that the cream is thick and difficult to use in the humid tropical climate, and nurses anecdotally suspect an increase in severe skin reactions during the summer months. Objective: This article presents the protocol for a randomized controlled trial that addressed a lack of evidence pertaining to the use of topical creams to prevent acute radiation skin reactions in a tropical climate. Methods: Two skin care creams were used in the trial. The trial's primary outcome measure was the incidence of moist desquamation during treatment and 1 month after treatment completion. The secondary outcome was the participants' acceptance of the allocated cream at similar time points. Results: Recruitment to the trial has been completed. Findings of the research will be reported in a separate publication. Conclusions: This article presents the protocol for a randomized controlled trial that addresses a lack of evidence pertaining to the use of topical creams to prevent acute radiation skin reactions in a tropical climate. Implications for Practice: This protocol can be adapted by other researchers conducting practice-based research.