The outpatient bone marrow biopsy and aspiration (BMBA) procedure performed with local anesthetic is often poorly tolerated in adults. This prospective, randomized, placebo-controlled, double-blind trial was designed to determine whether oral (p.o.) lorazepam and hydromorphone reduces pain and anxiety during BMBA. Eligible patients had lymphoma, had no prior BMBA, and were ≥ 18 years old. Since patients had bilateral BMBA, each served as their own control. Patients were stratified by anxiety level using the Spielberger Trait Anxiety Scale and randomized to: A) placebo for the first BMBA and 2 mg lorazepam and 2 mg hydromorphone p.o. for the contralateral BMBA, or B) placebo for both BMBAS. Changes in pain and anxiety experienced between the first and second BMBA were measured by the Visual Analogue Scale (VAS) and the Spielberger State Anxiety Scale at the time of the BMBA and 24 hours later. Twenty-seven patients were enrolled and 25 were evaluable; there were 17 males and eight females. The median age was 57 years (range, 28-79 years). Overall, BMBA was reported as painful in both arms, with a median VAS pain score after the second BMBA of 3.9 (scale, 0-10) for arm A and 5.8 for arm B (P = 0.21). There was no difference in the change in pain, anxiety, or recalled anxiety between treatment arms (all P values > 0.05). The difference in the change in recalled pain was of borderline significance (P = 0.07) and consistent with benzodiazepine-induced anterograde amnesia.