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Study Objective: To assess pain during and after diagnostic hysteroscopy in patients of reproductive age according to use of vaginal misoprostol., Design: A randomized, triple-masked, controlled clinical trial (Canadian Task Force classification I)., Setting: Diagnostic center at Instituto Materno Infantil de Pernambuco-Brazil., Patients: A total of 45 women of reproductive age underwent diagnostic anesthesia-free hysteroscopy., Interventions: In all, 400 mg of vaginal misoprostol or placebo was administered to randomized patients before diagnostic hysteroscopy., Measurements and Main Results: The clinical trial was interrupted in patients receiving misoprostol because of significant vaginal bleeding precluding the procedure (p = .0006). No significant difference existed in pain scores between the groups. Vaginal bleeding was the main side effect occurring in 11 patients of the misoprostol group. No vaginal bleeding occurred in the placebo group (p = .00002)., Conclusion: In the doses used, vaginal misoprostol induced vaginal bleeding and precluded diagnostic hysteroscopy in patients of reproductive age that limits continuation of this line of research. Further studies are needed to reassess the use of the drug in patients of this age group.