OBJECTIVE: Controversy exists regarding the use of oral contraceptives following hydatidiform mole and possible increased risk of persistent trophoblastic neoplasia. The purpose of this study is to perform a systematic review of the literature to assess the evidence for and against a possible link between oral contraceptive use and the need for chemotherapy after molar evacuation. METHODS: We searched the computerized databases MEDLINE, EMBASE, Popline, Web of Sciences, LILACS and the Cochrane Controlled Trials Register, ISI Proceedings, performed a hand search of references and wrote to experts to identify randomized controlled trials and observational studies comparing oral contraceptives with other methods of contraception. Quality assessment included: concealment of allocation; intention to treat analysis; plus attrition bias for trials; confounding factors and selection bias for observational studies. We collected or calculated risk ratios for the incidence of gestational trophoblastic neoplasia and hCG regression time associated with oral contraceptive use. RESULTS: Two randomized controlled trials were included for analysis. The risk ratios for OC use were similar in both studies: 0.69 (0.12-3.98) and 0.71 (0.46-1.10) respectively. No attempt to summarize these results was made because the studies observed different disease stages. In five of the seven observational studies, the risk ratio ranged from 0.57 (CI = 0.14-2.37) to 1.46 (CI = 0.56-3.79). CONCLUSION: No clear evidence for an association between oral contraceptive use during post-molar follow-up period and the incidence of gestational trophoblastic neoplasia was found. Practitioners should no longer avoid their use because of a supposed effect which we have shown here to be unsupported by evidence in the literature.