Background Prospective studies comparing the efficacy of selective versus nonselective alpha blockers for preoperative preparation of pheochromocytoma (PCC) are lacking. In this prospective nonrandomized study, we compared the outcome of preoperative preparation with phenoxybenzamine (PBZ) and prazosin (PRZ) in terms of perioperative hemodynamic alterations. Methods The study was conducted at a tertiary referral center from July 2010 to December 2012. Thirty-two patients with PCC underwent operation after adequate preparation with PBZ (n = 15) or PRZ (n = 17). Five pediatric and adolescent patients were excluded because of different hemodynamics in this population. Perioperative monitoring was done for pulse rate (PR) and blood pressure (BP) alterations, occurrence of arrhythmias, and time taken to achieve hemodynamic stability. Groups were compared with the Mann-Whitney test, Student's t test, and the v 2 test as applicable. Results Patients in the two groups were similar in age, gender, 24 h urinary metanephrine and normetanephrine levels, and type of procedure. Patients prepared with PRZ had significantly more intraoperative episodes of transient hypertension (systolic BP >= 160 mmHg) and hypertensive urgency (BP > 180/110 mmHg) (p 0.02, 0.03, respectively). More patients receiving PRZ suffered from transient severe hypertension (SBP >= 220 mmHg) (p 0.03). The PRZ group also had more median maximum SBP (233 mmHg vs PBZ 181.5 mmHg) (p = 0.01) and lesser median minimum SBP (71 mmHg vs PBZ 78 mmHg) (p 0.03). No significant differences were found between the study groups for changes in PR, postoperative BP alterations, occurrence of arrhythmias, and time taken to achieve hemodynamic stability. Conclusions PBZ was found superior to PRZ in having fewer intraoperative hemodynamic fluctuations.