The purpose of this study was to evaluate the effect of oral zinc sulfate in the prevention of chemotherapy-induced mucositis in patients undergoing hematopoietic stem-cell transplantation (HSCT). This study was a double-blind, randomized, placebo-controlled design, with 60 patients undergoing HSCT, divided proportionally in experimental group who received zinc sulfate, and in placebo group. They all had received high-dose chemotherapy conditioning regimen for allogenic transplantation. Oral mucositis assessed was based on World Health Organization (WHO) oral mucositis scale. There were no significant differences in the development of mucositis between the two groups. Severity of mucositis was not significantly different between the two groups either. The same result was obtained regarding the duration of mucositis. Zinc sulfate did not show any significant adverse effects in experimental group. In conclusion, Zinc sulfate did not have any clinical benefits in prevention or reduction of severity, and duration of high-dose chemotherapy-induced mucositis in patients undergoing HSCT. Copyright © 2011 John Wiley & Sons, Ltd.