Intraoperative hemodynamic instability is a major challenge during adrenalectomy for pheochromocytoma. Typically, pheochromocytoma is performed laparoscopically either through the retroperitoneal or transperitoneal approach. We aimed to determine if the operative approach affects intraoperative hemodynamic instability during surgery for pheochromocytoma in a large multicenter multicenter cohort. Retrospective, multicenter analysis of consecutive patients with pheochromocytoma who underwent total unilateral laparoscopic adrenalectomy without conversion were included. Statistical analysis was performed using established intraoperative criteria for intraoperative hemodynamic instability: 1) systolic blood pressure >160 mm Hg; 2) systolic blood pressure > 200 mm Hg; 3) mean arterial pressure <60 mm Hg; 4) systolic blood pressure >160 mm Hg + mean arterial pressure <60 mm Hg; and 5) systolic blood pressure >200 mm Hg + mean arterial pressure <60 mm Hg; and 6) intravenous vasopressor + vasodilator. In total, 341 patients met the inclusion criteria, 101 (29.6%) underwent retroperitoneal adrenalectomy and 240 (70.4%) transperitoneal adrenalectomy. Multivariate analysis showed that retroperitoneal adrenalectomy carries greater risk for mean arterial pressure <60 mm Hg (odds ratio 6.255, confidence interval 1.134–34.235, P = .035) compared with transperitoneal adrenalectomy. Overall and cardiovascular morbidity rates were comparable between the 2 approaches. The medical center was a significant independent influencing factor for all 6 intraoperative hemodynamic instability definitions. Variability in institutional management of pheochromocytoma intraoperatively has significant impact on all 6 intraoperative hemodynamic instability definitions. Standardization of anesthesia should be considered to reduce this variability.