IMPORTANCE Knowing the types and frequency of adrenal vein variants would help surgeons identify and control the adrenal vein during laparoscopic adrenalectomy. OBJECTIVES To establish the surgical anatomy of the main vein and its variants for laparoscopic adrenalectomy and to analyze the relationship between variant adrenal venous anatomy and tumor size, pathologic diagnosis, and operative outcomes. DESIGN, SETTING, AND PATIENTS In a retrospective review of patients at a tertiary referral hospital, 506 patients underwent 546 consecutive laparoscopic adrenalectomies between April 22, 1993, and October 21, 2011. Patients with variant adrenal venous anatomy were compared with patients with normal adrenal venous anatomy regarding preoperative variables (patient and tumor characteristics [size and location] and clinical diagnosis), intraoperative variables (details on the main adrenal venous drainage, any variant venous anatomy, duration of operation, rate of conversion to hand-assisted or open procedure, and estimated blood loss), and postoperative variables (transfusion requirement, reoperation for bleeding, duration of hospital stay, and histologic diagnosis). INTERVENTION Laparoscopic adrenalectomy. MAIN OUTCOMES AND MEASURES Prevalence of variant adrenal venous anatomy and its relationship to tumor characteristics, pathologic diagnosis, and operative outcomes. RESULTS Variant venous anatomy was encountered in 70 of 546 adrenalectomies (13%). Variants included no main adrenal vein identifiable (n = 18), 1 main adrenal vein with additional small veins (n = 11), 2 adrenal veins (n = 20), more than 2 adrenal veins (n = 14), and variants of the adrenal vein drainage to the inferior vena cava and hepatic vein or of the inferior phrenic vein (n = 7). Variants occurred more often on the right side than on the left side (42 of 250 glands [17%] vs 28 of 296 glands [9%], respectively; P = .02). Patients with variant anatomy compared with those with normal anatomy had larger tumors (mean, 5.1 vs 3.3 cm, respectively; P < .001), more pheochromocytomas (24 of 70 [35%] vs 100 of 476 [21%], respectively; P = .02), and more estimated blood loss (mean, 134 vs 67 mL, respectively; P = .01). For patients with variant anatomy vs those with normal anatomy, the rates of transfusion requirement (2 of 70 [3%] vs 10 of 476 [2%], respectively; P = .69) and reoperation for bleeding (1 of 70 [1%] vs 3 of 476 [1%]; P = .46) were similar between groups. CONCLUSIONS AND RELEVANCE Understanding variant adrenal venous anatomy is important to avoid bleeding during laparoscopic adrenalectomy, particularly in patients with large tumors or pheochromocytomas. Surgeons should anticipate a higher probability of adrenal vein variants when operating on pheochromocytomas and larger adrenal tumors.