In patients with primary hyperaldosteronism (PA), adrenal vein sampling (AVS) can identify patients suitable for unilateral adrenalectomy. However, in AVS with an indeterminate aldosterone-to-cortisol lateralization (ACL) ratio of 3.0-4.0, clinical guidance is unclear. The authors screened all patients undergoing AVS at the Cleveland Clinic from October 2010 to January 2021 and identified 18 patients with indeterminate ACL results. Ten underwent adrenalectomy and eight continued medical management. The surgical group was younger (58.5 vs. 68 years, p=.17), and more likely to have a unilateral imaging adrenal abnormality (90% vs. 38%, p=.043) and a lower contralateral suppression index (0.63 vs. 1.1, p=.14). Post-treatment, the surgical group had a significant reduction in diastolic blood pressure (-5.5mmHg, p=.043) and aldosterone (4.40 vs. 35.80ng/mL, p=.035) and required fewer anti-hypertensive medications (2 vs. 3, p=.015). These findings may support the benefit of adrenalectomy in a select group of patients with indeterminate ACL.