STUDY OBJECTIVE To evaluate the efficacy and safety of topical anesthesia in reducing pain and the frequency of vasovagal reactions during diagnostic hysteroscopy with endometrial biopsy in postmenopausal women. DESIGN Randomized, placebo-controlled, double-blind study. SETTING A university hospital. PATIENTS Forty-two postmenopausal women undergoing diagnostic hysteroscopy and endometrial biopsy. INTERVENTIONS Two milliliters of 2% mepivacaine or saline solution was injected transcervically into the uterine cavity before performing the procedures. MEASUREMENTS AND MAIN RESULTS Pain was evaluated on a visual analog scale, and heart rate and blood pressure were monitored continuously. Anesthesia reduced the pain experienced at hysteroscopy and endometrial biopsy, but not significantly. The frequency of vasovagal reactions was significantly lower in the anesthetized group. CONCLUSIONS Topical anesthesia effectively prevents the occurrence of vasovagal reactions in postmenopausal women undergoing hysteroscopy and endometrial biopsy.