Background: Surgery on pheochromocytoma carries a risk for hemodynamic (HD) instability. The aim of this study was to identify preoperative risk factors for intraoperative HD instability. In addition, efficacy of pretreatment with the α-adrenergic receptor (α) antagonists phenoxybenzamine (PXB) and doxazosin (DOX) was compared with respect to reduction of intraoperative HD instability. Methods: Seventy-three patients operated in Erasmus Medical Center between 1995 and 2007 were included. Parameters studied were catecholamine type and concentration, tumor diameter, mean arterial pressure (MAP) before and after (MAPα) pretreatment with α-antagonist, postural fall in blood pressure (BP) after pretreatment, type of α-blockade, type of operation, and presence of a familial polytumor syndrome. HD instability was assessed by measuring the number and time period MAP was below 60 mm Hg and systolic BP (SBP) was above 160 mm Hg. Results: A correlation was found between the intraoperative time periods of SBP above 160 mm Hg and plasma norepinephrine levels (r = 0.23; P < 0.05), tumor diameter (r = 0.36; P < 0.01), and postural BP fall (r = 0.30; P < 0.05).MAPat presentation and after α-blockade above 100 mm Hg (BP, 130/85 mm Hg) was related to more and longer episodes with a SBP above160 mm Hg (P < 0.01). Type of operation or α-blockade and presence of a familial polytumor syndrome were not related to intraoperative HD instability. Postoperative MAP was lower in the DOX group than in the PXB group (P < 0.05). Conclusion: Risk factors for HD instability during surgery for pheochromocytoma include a high plasma NE concentration, larger tumor size, more profound postural BP fall after α-blockade, and a MAP above 100 mm Hg (130/85 mm Hg). Efficacy for preventing HD instability was identical for PXB and DOX. Copyrigh