BACKGROUND: Adrenal vein sampling (AVS) is the gold standard for diagnosing the dominant side in patients with primary aldosteronism (PA). encodes aldosterone synthase. The aim of this study was to investigate the prognosis of dominant-side adrenalectomy in patients with PA identified by AVS in the context of aldosterone synthase expression in the postoperative pathology of those patients. METHODS: This retrospective study included 73 PA patients who underwent AVS followed by unilateral adrenalectomy. Patients were categorized into AVS bilateral success group, AVS unilateral success group, and AVS bilateral failure group based on their AVS status. Immunohistochemistry (IHC) for CYP11B2 was combined with postoperative pathology in these patients, and the clinical and biochemical prognosis of these patients was assessed 6 months after adrenalectomy. RESULTS: Between September 2023 and September 2024, 73 patients underwent unilateral adrenalectomy guided by AVS at our institution, with CYP11B2 IHC successfully performed in 63 cases. Among these, 21 patients (33.33%) achieved bilateral AVS success, 20 (31.75%) demonstrated unilateral AVS success, and 22 (34.92%) exhibited bilateral AVS failure. Pathological analysis of the bilateral AVS success group revealed aldosterone-producing adenoma (APA) in 12 cases, aldosterone-producing micronodule (APM) in 1, multiple-aldosterone-producing micronodules/nodules (MAPM/MAPN) in 2, aldosterone-producing diffuse hyperplasia (APDH) in 1, APA with MAPM in 3, and APA with APDH in 2. In this group, complete and partial clinical success rates were 47.62% (10/21) and 52.38% (11/21), respectively, while biochemical success rates reached 95.24% (20/21) for complete and 4.76% (1/21) for partial success. The unilateral AVS success cohort included APA (n=8), aldosterone-producing nodule (APN) (n=2), MAPM/MAPN (n=3), APA with MAPM (n=4), APA with APDH (n=2), and 1 CYP11B2 IHC-negative lesion, with clinical success rates of 40.00% (8/20) complete and 60.00% (12/20) partial, alongside 90.00% (18/20) complete and 10.00% (2/20) partial biochemical success. The bilateral AVS failure group comprised APA (n=8), MAPM/MAPN (n=1), APA with MAPM (n=5), APA with APDH (n=2), and 6 CYP11B2 IHC-negative lesions, demonstrating 36.36% (8/22) complete, 50.00% (11/22) partial, and 13.64% (3/22) no clinical success, with biochemical outcomes of 72.73% (16/22) complete, 18.18% (4/22) partial, and 9.09% (2/22) no success. Notably, bilateral AVS success correlated with significantly superior biochemical outcomes compared to bilateral failure (P=0.045). CONCLUSIONS: Adrenalectomy guided by AVS yields better outcomes in patients with PA when AVS is successful on both sides compared to those with bilateral AVS failure. The source of excess aldosterone secretion on the dominant side identified by AVS is not necessarily an APA/APN. It may also include MAPM/MAPN, diffuse adrenal cortical hyperplasia, and various complex combined conditions. In patients with bilateral AVS failure, adrenal specimens more frequently exhibit negative immunohistochemical staining for CYP11B2.