Early identification of high risk molar pregnancy is important in preventing the development of subsequent postmolar trophoblastic disease (PMTD). In the present study, evaluation of risk factors of developing PMTD, and indications for initiating prophylactic chemotherapy, and investigation of the effects of prophylactic chemotherapy were undertaken. One hundred and forty complete molar pregnancies treated at Yonsei University College of Medicine were retrospectively analyzed. Thirty-six cases of PMTD developed in these molar pregnancies during follow-up. Risk factors for PMTD were ranked according to frequency with which they were associated with PMTD. The patients with no risk factors were classified in the low-risk group, with one or two in the medium-risk group, and with three or more in the high-risk group. Prophylactic chemotherapy was administered to 14 of 52 low-risk, to 21 of 46 medium-risk, and to 17 of 42 high-risk patients. Among the high-risk patients, the time required for remission was significantly shorter in the group with prophylactic chemotherapy (13.5 weeks) than in the group without prophylactic chemotherapy (22.4 weeks). There were no differences in the duration until remission among the low- and medium-risk patients. Of the 52 patients who received prophylactic chemotherapy, 8 (15.4%) developed PMTD. Among the high-risk patients the occurrence of PMTD was significantly lower in the prophylactic chemotherapy group. Among the low-risk and medium-risk patients, there were no differences in the occurrence of PMTD between the chemoprophylaxis treated and untreated groups. Our results strongly support the use of prophylactic chemotherapy for patients that were designed under our high risk criteria. Prophylactic chemotherapy helps to prevent or reduce the risk of developing PMTD, and shorten the time required for complete remission in high-risk patients.