Post-operative hypoparathyroidism (PoHypo) is the most common cause of hypoparathyroidism and it is the result of accidental parathyroid removal/injury during neck surgery. The lack of PTH alters calcium homeostasis and patients are at risk of renal complications, bone involvement, infections and psychiatric syndromes. Conventional therapy, that includes calcium supplements and activated vitamin D, does not restore the complete calcium homeostasis. From a neuropsychological point of view, patients complain with neurocognitive symptoms such as “brain fog”, impaired ability to focus, memory loss, depression. Poor quality of life (QoL), evaluated by non-specific questionnaires, has been demonstrated in these patients. The aim of this study is to evaluate the cognitive function by neuropsychological specific tests in patients with PoHypo and matched controls and their relationship with biochemical parameters. This is a prospective monocentric study; we enrolled outpatients who underwent total thyroidectomy for malignant cured disease, 34 with chronic (>6 months) PoHypo (mean age 50.7 ys) and 31 without PoHypo (mean age 49.9 ys). The two groups did not differ significantly in TSH; PoHypo group had a relatively controlled serum calcium adjusted for albumin (SAlbCa) levels in therapy (mean 8.8±0.1mg/dl, 4 patients with <8.2 mg/dl) and control group had normal SAlbCa levels (9.4 ±0.2mg/dl). In PoHypo patients a significant correlation was found between serum calcium, SAlbCa levels and the scores at the Trail-Making Test_A (a specific test evaluating attention capacity; r= -0.36; p<.05, r= -0.37; p<.05) and at the Semantic Fluency Test (validated for cognitive function; r= 0.32; p<.05, r= 0.34; p<.05). No significant correlations were found in the control group. A median split based on serum calcium levels (> or < than 9 mg/dl) was performed in both patients groups. PoHypo patients with serum calcium levels <9 mg/dl performed worse than PoHypo patients with calcium>9mg/dl, either at the Trail-Making Test_A (scores:34.00 vs 21.05, p<.05) and Semantic Fluency Test (39.62 vs 47.4, p<.05). Moreover, PoHypo patients with serum calcium <9 mg/dl performed worse than matched control patients, either at the Trail-Making Test_A (scores:34.00 vs 27.61, p<.05) and Semantic Fluency Test (39.62 vs 46.16, p<.05). These findings suggest that PoHypo patient’s performance in cognitive tests is worse than matched controls and that this is correlated with serum calcium levels.