Severe hypocalcaemia following parathyroidectomy for secondary or tertiary hyperparathyroidism (SHPT/THPT) is scarcely studied. We aimed to describe and identify risk factors for early and persistent hypocalcaemia after parathyroidectomy. Retrospective pair-matched cohort study. We assessed 87 dialysis patients with SHPT (n = 73) or THPT (n = 14) paired with 146 subjects with primary hyperparathyroidism (PHPT) who underwent parathyroidectomy and were followed for 12 months. Early severe hypocalcaemia was defined as a free Ca ≤0.8 mmol/L [3.2 mg/dl] or corrected Ca ≤1.87 mmol/L [7.5 mg/dl] within 48 h. After parathyroidectomy and persistent hypocalcaemia, as an elemental Ca intake >3.0 g/day to achieve corrected Ca >2 mmol/L [8.0 mg/dl]. Early severe hypocalcaemia occurred in 77% (67/87) versus 6.8% (10/146) of subjects with SHPT/THPT and PHPT, respectively (p < .001). In SHPT/THPT cases, persistent hypocalcaemia occurred in 77% (49/64) and 64% (35/54) after 6 and 12 months of parathyroidectomy, respectively. In PHPT cases, persistent hypocalcaemia occurred in 6.8% (10/146) after 4-12 months of parathyroidectomy. Preoperative serum alkaline phosphatase (ALP) was the only risk factor associated to early severe hypocalcaemia (OR 7.3, 95% C.I. 1.7-10.9, p = .006) and persistent hypocalcaemia (OR 7.1, 95% C.I: 2.1-14.2, p = .011). Subjects with persistently low intact parathormone (iPTH) (<5.3 pmol/L [50 ng/ml]), suggestive of adynamic bone disease) showed higher Ca increases and less oral calcium requirements compared to those who progressively increased iPTH after parathyroidectomy. Early and persistent hypocalcaemia after parathyroidectomy in severe HPT were a common event associated directly to preoperative ALP levels. Subjects with persistently low postoperative iPTH normalized serum Ca more frequently after 1 year of follow up.