The standard procedure for percutaneous liver biopsy (PLB) involves only the use of local anesthesia. However, at times, a PLB can be frightening and uncomfortable. Such experiences often limit the willingness of patients to undergo subsequent follow-up biopsies. To investigate the ability of midazolam, a new water-soluble benzodiazepine preparation, noted for its potency, rapid onset of action, and amnestic qualities, to enhance patient acceptability of a follow-up liver biopsy, a “sedative dose” of midazolam (2 mg) or saline was administered immediately prior to and following a percutaneous liver biopsy. The initial dose was used to sedate the subject while not impairing patient cooperation during the biopsy procedure; the second dose was used to induce amnesia for the biopsy procedure. The next morning patient recollection for the preceding biopsy procedure and their willingness to undergo a future PLB were assessed using a questionnaire. Forty-one patients (ages 18–78) were randomized to receive either midazolam (N=21) or saline/ placebo (N=20) treatment. All PLBs were obtained with a Trucut needle. All subjects were given 2–5 cc of 2% xylocaine local anesthetic at the biopsy site. The questionnaire utilized evaluated patient experience of the procedure with respect to their recall, level of anxiety during the procedure, and willingness to undergo a repeat procedure. The data obtained revealed that those receiving midazolam admitted to experiencing less discomfort during the biopsy procedure (P<0.04) and had less memory for the procedure (P<0.001). More importantly, 79% of those receiving midazolam stated they would have little or no trouble undergoing a subsequent PLB as compared to 55% of those given saline. These data suggest that midazolam (1) reduces subject anxiety and perceived discomfort before and during PLB; (2) produces partial amnesia for the biopsy experience; and (3) thereby may improve patient acceptance of follow-up liver biopsies should such be required.