Randomized trials have shown that sucralfate is effective in the management of acute radiation reactions such as oesophagitis, mucositis and proctitis. However, at the time of commencement of the present trial, it had never been used in the management of moist desquamation of the skin. The purpose of the present study was to assess the value of sucralfate cream in the management of moist desquamation during radiotherapy. Patients who developed moist desquamation during radiation were eligible. Patients were stratified by site of radiotherapy into three groups: (i) the head and neck; (ii) the breast; and (iii) other sites. Patients were randomized to receive 10% sucralfate in sorbolene cream or sorbolene alone. Patients' pain and skin healing were assessed by using linear analogue self-assessment (LASA) scales and by serial measurement of the desquamated area. Due to poor patient accrual, the trial was terminated after 2 years and 39 patients. No statistically significant difference was found between the two arms in either time from randomization to healing or improvement in pain score. Twenty patients in the sucralfate arm took a geometric mean of 14.8 days to heal whereas 19 patients receiving sorbolene alone took a geometric mean of 14.2 days. The ratio of mean times of healing, 1.043, is not statistically different from 1 (P = 0.86; 95% CI = 0.65, 1.67). A total of 75% of the patients reported pain relief on application of either cream. Mean LASA scores for pain for each day after randomization were compared by treatment arm and there was no statistically significant difference (P = 0.32). The present trial was unable to show a difference in terms of time to healing or pain relief in the treatment of moist desquamation. The small number of patients in the trial gave a wide confidence interval for treatment difference, implying that an important effect of sucralfate has not been excluded. Given the poor accrual in the present, single-institution study, future studies may need to be multi-institutional and we encourage other centres to perform randomized trials in the management of moist desquamation.