Objective <p>This study aimed to compare the accuracy of adrenal vein sampling (AVS) and ⁶⁸Ga-Pentixafor positron emission tomography (PET)/computed tomography (CT) in predicting the functional outcome from adrenalectomy in patients with primary aldosteronism (PA), and to investigate the utility of ⁶⁸Ga-Pentixafor PET/CT in laparoscopic partial adrenalectomy.</p> Methods <p>We prospectively enrolled patients diagnosed with PA. All patients underwent ⁶⁸Ga-Pentixafor PET/CT and AVS. Patient management was discussed by a multidisciplinary team. Ninety surgically eligible patients were randomized to partial (<i>n</i> = 45) or total adrenalectomy (<i>n</i> = 45), while 97 received medical therapy. Postoperative Aldosterone Surgical Outcome (PASO) criteria served as the gold standard.</p> Results <p>In total, 187 patients with PA were examined using ⁶⁸Ga-pentixafor PET/CT and AVS, and 90 patients who underwent surgery were included in the analysis. The accuracy of ⁶⁸Ga-Pentixafor PET/CT in correctly predicting biomedical partial or complete success, biomedical complete success, clinical partial or complete success, and clinical complete success was 78.89%, 77.78%, 77.67%, and 67.78%, respectively. For AVS, the accuracies were 74.44%, 73.33%, 70.00%, and 54.44%, respectively. ⁶⁸Ga-pentixafor PET/CT was not significantly superior, but the differences lay within the pre-specified − 10% margin for non-inferiority. Functional outcomes did not significantly differ between the partial and total adrenalectomy groups. Multivariable logistic analysis demonstrated that the lower highest systolic blood pressure and higher SUVmax were independent factors of complete clinical success. The AUC for SUVmax in determining clinical complete success was 0.896, with an optimal cutoff value of 9.8. Subgroup analysis showed no functional outcome difference between laparoscopic partial and total adrenalectomy for patients with an SUVmax over 9.8. However, for those with an SUVmax below 9.8, laparoscopic total adrenalectomy yielded better results than laparoscopic partial adrenalectomy.</p> Conclusion <p>The accuracy of ⁶⁸Ga-Pentixafor PET/CT is comparable to the conventional, invasive method of AVS in forecasting the functional outcomes of adrenalectomy. SUVmax is an independent factor in determining complete clinical success and can potentially predict the functional outcome of laparoscopic adrenalectomy. It is suggested that laparoscopic partial adrenalectomy be performed on individuals who present an SUVmax value exceeding 9.8. The ability of ⁶⁸Ga-Pentixafor PET/CT to localize aldosterone-producing adenoma ultimately paves the way for the use of more focal treatment options.</p> Trial registration <p>ChiCTR2300070830. Registered 23 April 2023.</p> Graphical Abstract <p></p>