Abstract Context Primary aldosteronism (PA) represents a secondary form of arterial hypertension that can be cured by surgery. Evidence of adrenal insufficiency (AI) was recently found in patients with PA who had undergone unilateral adrenalectomy (uADX). Objective To study the incidence and long-term outcome of postoperative AI after uADX for PA. Design Prospective registry study (August 2014 until the end of 2018). Setting Tertiary referral center. Patients One hundred consecutive patients undergoing uADX for PA were included. All patients underwent postoperative ACTH stimulation testing. Intervention Postoperative ACTH stimulation testing to identify patients with AI. Main Outcome Measures Incidence of patients with postoperative AI and definition of long-term outcome. Results Twenty-seven percent of patients developed postoperative AI. Of these, 48% had postoperative ACTH stimulation serum cortisol levels ≤13.5 µg/dL (severe AI); 52% were classified into the group with moderate AI (stimulated serum cortisol levels: 13.5 to 17 µg/dL). Patients with severe AI required significantly longer hydrocortisone replacement therapy than the moderate group (median [25th, 75th percentiles]: 353 [294, 476] days; 95% CI: 284 to 322 days; vs 74 [32, 293] days; 95% CI: 11 to 137 days; P = 0.016). One patient with severe AI was hospitalized for an acute adrenal crisis. With a cumulative follow-up of 14.5 years, this produced an incidence rate of 6.9 adrenal crises per 100 patient-years. Conclusion We suggest performing postoperative ACTH stimulation tests in all patients who undergo uADX for PA.