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Context: The role of cytoreduction of adrenocortical carcinoma (ACC) remains poorly understood., Objective: To analyze the impact of cytoreductive surgery of the primary tumor in patients with metastatic ACC., Design and Setting: We performed a multicentric, retrospective paired cohort study comparing the overall survival (OS) in patients with metastatic ACC who were treated either with cytoreductive surgery (CR group) or without cytoreductive surgery (no-CR group) of the primary tumor. Data were retrieved from 9 referral centers in the American-Australian-Asian Adrenal Alliance collaborative research group., Patients: Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between January 1, 1995, and May 31, 2019., Intervention: Performance (or not) of cytoreductive surgery of the primary tumor., Main Outcome and Measures: A propensity score match was done using age and the number of organs with metastasis (≤2 or >2). The main outcome was OS, determined from the date of diagnosis until death or until last follow-up for living patients., Results: Of 339 patients pooled, 239 were paired and included: 128 in the CR group and 111 in the no-CR group. The mean follow-up was 67 months. Patients in the no-CR group had greater risk of death than did patients in the CR group (hazard ratio [HR] = 3.18; 95% CI, 2.34-4.32). Independent predictors of survival included age (HR = 1.02; 95% CI, 1.00-1.03), hormone excess (HR = 2.56; 95% CI, 1.66-3.92), and local metastasis therapy (HR = 0.41; 95% CI, 0.47-0.65)., Conclusion: Cytoreductive surgery of the primary tumor in patients with metastatic ACC is associated with prolonged survival., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)