Context: Many patients with unilateral primary aldosteronism (PA) have normal adrenal imaging, but little is known about their outcome following adrenalectomy., Objective: To evaluate biochemical and clinical outcomes after adrenalectomy in patients with unilateral PA and normal-appearing adrenal imaging., Design: Retrospective cohort study of patients seen between January 2006 and May 2018., Setting: A Canadian tertiary care PA referral center., Patients: Consecutive individuals with PA, normal cross-sectional adrenal imaging, and lateralizing adrenal vein sampling (AVS) who underwent adrenalectomy during the study period., Primary Outcome: Biochemical response to adrenalectomy graded according to the Primary Aldosteronism Surgical Outcome criteria., Results: A total of 40 patients were included. Biochemical outcomes were available for 33 people (mean age, 54.7 years; 91% male; median follow-up, 2.7 months), with 28 (85%) showing a complete or partial response and 5 (15%) with no response. Clinical outcomes were available for 36 people (mean age, 54.6 years; 86% male; median follow-up, 9.8 months), with 31 (86%) demonstrating a complete or partial response and 5 (14%) with no response., Conclusions: The prognosis after adrenalectomy is highly favorable for patients with unilateral PA and normal-appearing adrenal imaging. Patients with lateralizing disease should be considered for surgery despite apparently normal adrenal imaging., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)