Despite the significant life saving effects of chemotherapeutic drugs in patients with blood malignancies, there has been a high rate of side effects on oral mucosa reported in the literature. A randomized controlled double-blind clinical trial in 1995 was designed to evaluate the preventative effects of a 002% Chlorhexidine Gluconate on oral complication.A group of 45 diagnosed acute leukemic patients (69% male and 31% female, mean age 25.9±905) were selected for this study who were reffered to three major hospitals in Tehran, namely: Imam Khomeini, Shariati and Modarres General Hospitals. None of the subjects used any mechanical too for oral hygiene. Patients were clinically assessed prior to the chemotherapy and at 1, 2, 3, 4 weeks post therapy, by their plaque index, gingival index, mucosa status, and colour of the teeth. A swab sample was taken from oral mucosa for paraclinical evaluation. Subjects were divided into experimental and control groups, randomly the experimental group received Chlorhexidine Gluconate 0.02% oral rinse and the control group were given a placebo.Results revealed that the experimental group showing a significant reduction in plaque index, gingival index and mucositis (P<0.025). Only dental colour index was increased. Paraclinical indices including total bacterial count, Staphilococci SP, Streptococci SP and Candida colony count were decreased in experimental group (P<0.0.1).In conclusion: Chlorhexidine showed to be effective in reducing oral complications of chemotherapy.