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Objectives: To evaluate the efficacy and safety of performing a fluoroscopically guided bone marrow aspiration and biopsy (BMAB) using a drill-powered needle in a large patient population., Methods: This retrospective study received institutional review board approval with a waiver of patient informed consent. We identified all BMAB procedures from August 2012 through December 2016 performed at our institution using fluoroscopic guidance and a drill-powered needle. Clinical diagnosis, patient age, patient gender, biopsy site, biopsy needle gauge, bone marrow aspirate volume, bone marrow core biopsy length, patient platelet count, conscious sedation details, complications, and diagnostic adequacy were investigated for each case and summarized., Results: A total of 775 BMAB procedures were performed and analyzed. These were performed in 436 female patients and 339 male patients ranging in age between 16 and 91 years (average age of 53 years). Samples obtained from the procedures in our series were diagnostic in 95.0% of cases. The complication rate for our series was 0.3%., Conclusions: The use of fluoroscopic guidance and a drill-powered needle for bone marrow aspiration and biopsy is a safe and efficacious procedure., Key Points: • Fluoroscopy can be utilized for imaging guidance during bone marrow aspiration and biopsy. • The use of fluoroscopic guidance and a drill-powered needle for bone marrow aspiration and biopsy has a high diagnostic yield. • The procedure has an excellent patient safety profile.