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To determine the association between preoperative hematocrit level and risk of blood transfusion for laparotomic and laparoscopic myomectomy based on myoma burden and surgical route.A cohort study of prospectively collected data.American College of Surgeons National Surgical Quality Improvement Program participating institutions.A total of 26 229 women who underwent a laparotomic or laparoscopic myomectomy from 2010 to 2020.The primary outcome assessed was the risk of transfusion based on preoperative hematocrit level. This was evaluated with respect to myoma burden and surgical route.There were 26 229 women who underwent a myomectomy during the study interval, 2345 women (9%) of whom required a blood transfusion. Compared with patients who did not require transfusion, those who did had lower median preoperative hematocrit levels (34.7 vs 38.2). Patients were stratified by surgical approach (laparotomic vs laparoscopic) and myoma burden (1-4 myomas/weight ≤250 g or ≥5 myomas/weight250 g) using Current Procedural Terminology codes (58140, 58146, 58545, 58546). In all categories, there was an inverse relationship between blood transfusion and preoperative hematocrit level with increasing risk depending on preoperative hematocrit range. The odds ratios comparing hematocrit level of 29% with 39% were 6.16 (95% confidence interval [CI], 5.15-7.36), 4.92 (95% CI, 4.19-5.78), 4.85 (95% CI, 3.72-6.33), and 5.2 (95% CI, 3.63-7.43) for patients with laparotomic (1-4 myomas/≤250 g, ≥5 myomas/250 g) and laparoscopic myomectomy (1-4 myomas/≤250 g, 5 myomas/250 g), respectively.Incremental increases in hematocrit result in a significantly decreased risk of blood transfusion at the time of myomectomy.