Adrenalectomy for pheochromocytoma is considered to be a challenging procedure because of the risk of hemodynamic instability (HI), which is poorly defined and unpredictable. The objective of this retrospective study from a prospectively maintained database was to determine the predictive factors for perioperative HI, which is defined as a morbidity-related variable, in patients undergoing unilateral laparoscopic adrenalectomy (LA) for pheochromocytoma. A total of 149 patients with unilateral pheochromocytoma undergoing LA were included. First, HI was defined using independent hemodynamic variables associated with perioperative morbidity. Next, a multivariable logistic regression analysis was performed to determine the independent preoperative risk factors for HI. There was no postoperative mortality, and the overall morbidity rate was 10.7 %. The use of a cumulative dose of norepinephrine >5 mg was the only independent hemodynamic predictive factor for postoperative complications; thus, this variable was used to define HI. A multivariate analysis revealed that a symptomatic high preoperative blood pressure (p = 0.003) and a ten-fold increase in urinary metanephrine and/or normetanephrine levels (p < 0.0001) were significant predictors of HI. When no predictive factors were present, the risk of HI and the postoperative morbidity were 1.5 and 4.3 %, respectively. However, when two predictive factors were present, the HI risk and the postoperative morbidity were 53.8 and 30.8 %, respectively. Perioperative HI, defined as the need for a cumulative dose of norepinephrine >5 mg, is significantly associated with postoperative morbidity and can be predicted by symptomatic preoperative high blood pressure and above a ten-fold increase in urinary metanephrine and/or normetanephrine levels.