Purpose <p>Bone marrow biopsy (BMB) is a common procedure for the diagnosis, staging, and evaluation of several hematological diseases. BMB often causes anxiety and pain even when local anesthesia (LA), premedication, or an equimolar mixture of oxygen and nitrous oxide (EMONO) are used. Hypnosis has emerged as a promising non-pharmacological method to reduce anxiety and pain during invasive procedures. QUALHYBOM, a prospective, multicenter, randomized, open-label study was conducted to assess whether adding hypnosis to LA (LA + H) could improve patient comfort during BMB compared to LA alone.</p> Method <p>QUALHYBOM included 180 BMB-naive patients with suspected or confirmed hematological disorders, randomized (LA group <i>n</i> = 91, LA + H group <i>n</i> = 89) from June 2023 to November 2024 across four French hematological departments. The primary endpoint was patient comfort rated on a scale from 0 (no comfort) to 10 (maximum comfort), evaluated immediately after the procedure. Secondary outcomes included pain, anxiety (before and after BMB), practitioner comfort, and use of EMONO.</p> Results <p>Patient groups were well-matched at enrolment. Median comfort scores were 9 vs. 5, pain scores 2 vs.6, and post-procedure scores 1 vs.5, in the LA + H vs.LA groups, respectively, both with <i>p &lt; </i>10⁻⁴. Finally, the operator comfort was higher (10 vs. 7), and EMONO requirement lower (3% vs. 29%) in the LA + H group, both with <i>p</i> &lt; 10⁻⁴.</p> Conclusion <p>These findings suggest that hypnosis significantly enhances patient comfort and key procedural parameters during BMB, warranting its consideration as addition to local anesthesia. Its integration into clinical practice may reduce the need for supplementary pharmacological interventions, including EMONO.</p> Trial registration <p>ClinicalTrials.gov Identifier NCT05178849.</p>