BACKGROUND: Neuropsychiatric disorders frequently manifest in primary hyperparathyroidism (PHPT), yet evidence of parathyroidectomy's benefit remains mixed. We sought to compare the incidence of neuropsychiatric disorders among patients treated with parathyroidectomy versus nonoperative management. METHODS: We retrospectively reviewed our institutional administrative database for patients with PHPT. Patients with secondary hyperparathyroidism were excluded. The date of biochemical diagnosis of PHPT was designated as day 0 and new-onset neuropsychiatric disorders were defined as conditions diagnosed after this date. The risk of new-onset neuropsychiatric disorders in propensity score-matched surgical and nonsurgical patients was compared using the Cox regression over a median follow-up of 4.2 years. RESULTS: Our cohort included 3728 patients, predominantly female (78%) and white (63.9%), with a mean (± Standard deviation) age of 62 ± 14 years. Of these, 1704 (45.7%) underwent parathyroidectomy. After propensity score matching and adjusting for clinical characteristics, patients who had parathyroidectomy showed a reduced hazard ratio (HR) for new-onset cognitive impairment (HR: 0.65, 95% CI: 0.47-0.91), somnolence (HR: 0.45, 95% CI: 0.23-0.9) and schizophrenia (HR: 0.08, 95% CI: 0.01-0.6), but not for anxiety (HR: 1.07, 95% CI: 0.83-1.37), depression (HR: 1.02, 95% CI: 0.77-1.36) or suicidal ideation (HR: 0.31, 95% CI: 0.04-2.71). Additionally, surgical patients were less likely to require inpatient care (0.3% vs. 1.8%, p <
0.002) for neuropsychiatric disorders. CONCLUSIONS: Parathyroidectomy is associated with lower risks of new-onset cognitive impairment, schizophrenia, or somnolence, indicating potential benefit of operative management in improving neuropsychiatric symptoms in patients with PHPT.