Purpose <p>Expression of CXC chemokine receptor 4 (CXCR4) has proved to be a valuable tool for guiding the diagnosis and treatment of aldosterone-producing adenoma (APA). In this study, we evaluated whether CXCR4 imaging with ⁶⁸Ga-pentixafor PET/CT shows significant changes after superselective adrenal artery embolization (SAAE).</p> Methods <p>We prospectively recruited 25 patients with clinically diagnosed APA. All patients were examined with ⁶⁸Ga-pentixafor PET/CT and adrenal venous blood sampling (AVS) before and after SAAE. PET/CT showed that the tracer uptake of unilateral nodular adrenal gland was higher than that of normal adrenal tissue. AVS showed that the dominant secretory side was consistent with that on PET/CT. All patients were successfully treated with SAAE. Clinical follow-up was carried out according to primary aldosteronism surgical outcome (PASO) criteria, and included monitoring of drug type, blood pressure, serum potassium, and aldosterone/renin ratio to evaluate surgical effect. Post operation ⁶⁸Ga-pentixafor PET/CT and the maximum standardized uptake value (SUVmax) were used to observe the uptake of adrenal lesions after SAAE.</p> Results <p>Among the 25 APA patients who successfully underwent SAAE, 14 were men and the average age was 51.88 ± 8.89 years. The consistency between AVS and ⁶⁸Ga-pentixafor PET/CT reaches 100%. Before operation, the SUVmax of the diseased side (16.79 ± 2.51, <i>n</i> = 25) was significantly higher than that of the non-diseased side (4.56 ± 0.57, <i>P</i> &lt; 0.01). According to PASO criteria, 13 of 25 patients achieved complete clinical remission, 9 achieved partial remission and the treatment was ineffective for three patients. 19 cases achieved biochemical complete remission and 3 cases achieved partial remission. Following the treatment, 22 patients showed complete or partial remission. The ⁶⁸Ga-pentixafor SUVmax of the diseased side decreased significantly (16.75 ± 2.54 vs. 4.37 ± 1.52, <i>n</i> = 22, <i>P</i> &lt; 0.001). For the patients who ineffective to the treatment, the SUVmax did not change (17.07 ± 2.72 vs. 16.17 ± 2.72, <i>n</i> = 3, <i>P</i> = 0.842). The 25 patients were divided into two groups according to the average value (≥ 65% and &lt; 65%) of the decrease in SUVmax. The decrease in SUVmax correlated with a good patient prognosis under the PASO standard (<i>P</i> = 0.009).</p> Conclusion <p>A decrease in SUVmax is related to the prognosis. CXCR4 imaging with ⁶⁸Ga-pentixafor can be used for pre- and post-SAAE evaluation in patients with APA.</p>