Background Despite significant advances in imaging and genetics, as well as surgical and anesthetic innovations, morbidity in pheochromocytoma surgery remains significant. The aim of this study was to identify the predictive factors of global and cardiovascular morbidity following unilateral laparoscopic adrenalectomy for pheochromocytoma. Methods We conducted a retrospective study from a unicentric cohort. All patients who underwent non-converted laparoscopic unilateral adrenalectomy for pheochromocytoma between 2000 and 2017 were included. Our patients did not systematically benefit from preoperative pharmacological preparation. It is to be noted that they never received alpha-blockers. Preoperative, intraoperative, and postoperative data during follow-ups were collected. Univariate and multivariate analyses by logistic regression were performed. Results A total of 134 patients were included. Fifty-three percent of patients did not receive preoperative pharmacological preparation (PPP) and 33% neither preoperative antihypertensives nor PPP before surgery. There was no postoperative mortality. The global morbidity was 13.4%, while cardiovascular morbidity was 4.5%. The main factors associated with global morbidity were preoperative diuretics, a medical history of stroke, and the need for pressor amines postoperatively. The main factor associated with cardiovascular morbidity was the need for pressor amines postoperatively. Predictive factors of postoperative need for pressor amines for hypotension were the tumor size, preoperative beta-blockers, and/or diuretics. Conclusion In this large cohort of patients, our data revealed no mortality and low global and cardiovascular morbidity rates, showing that pheochromocytoma surgery without systematic PPP and even without preoperative antihypertensives is feasible and safe for selected patients. Our data also highlight the need for a good preoperative evaluation of the patient and the tumor, in order to optimize treatments and to help the detection of high-risk patients. This also allows us to better prevent and anticipate their possible complications.