Objective: Around 15-28% of hydatidiform mole patients suffer from malignant degeneration following evacuation. Since retinoic acid can control cell proliferation and stimulate apoptosis, vitamin A could be used as a therapy for preventing such malignant transformation. The objective of this study was to demonstrate the use of vitamin A as a chemoprevention following hydatidiform mole development. Materials and methods: The study made use of a randomized clinical trial, double blind protocol. Subjects were patients with complete hydatidiform moles, not receiving cytostatics. The intervention was administration of placebo or vitamin A at 200,000 IU per day, performed until the patients were declared as having recovered or having malignant trophoblastic disease (MTD). The outcome variables were the incidence of regression and MTD, established based on WHO criteria. Results: At clinical trial as many as 67 cases met the requirements for the study. Two cases were lost from observation and three experienced pregnancy. The incidence rate of malignant trophoblastic disease in the control group was 28.6%, and in the therapy group was 6.3%. No difference was found in the changes of SGOT and SGPT levels of the therapy group compared with the control group. Conclusion: The rate of malignant trophoblastic disease (MTD) was reduced in the group receiving vitamin A therapy.