Objective  To explore the risk factors of severe hypocalcemia in patients with renal secondary hyperparathyroidism (SHPT) after parathyroidectomy (PTX).  Methods A retrospective study was conducted on 784 patients with renal SHPT who underwent total parathyroidectomy and autologous transplantation (TPTX+AT) or total parathyroidectomy (TPTX). Patients were divided into severe hypocalcemia group (corrected serum calcium ＜1.8 mmol/L) and non-severe hypocalcemia group (corrected serum calcium ≥1.8 mmol/L) according to the serum calcium level at the first day after operation.  Results  There were 214 cases (27.3%) with severe hypocalcemia at the first day after PTX. Age (t=5.648, P＜0.001), dialysis age>5years  (Z=7.199, P=0.007), peritoneal dialysis (c2=4.985, P=0.026), preoperative hypocalcemia (c2=6.241, P=0.012), preoperative parathyroid hormone (PTH) level (Z=-8.902, P＜0.001), preoperative alkaline phosphatase (ALP) level (Z=-10.230, P＜0.001) and postoperative serum phosphorus reached the standard level (c2=3.988, P=0.046) were different between severe hypocalcemia group and non-severe hypocalcemia group. Multivariate logistic regression showed that younger age (OR=0.963, 95% CI 0.945~0.980, P＜0.001), preoperative hypocalcemia (OR=1.930, 95% CI 1.120~3.327, P=0.018), preoperative higher PTH level (OR=1.0004, 95% CI 1.000~1.001, P=0.016) and preoperative higher ALP level (OR=1.001, 95% CI 1.000~1.001, P=0.001) were the independent risk factors of severe hypocalcemia in renal SHPT patients after PTX.  Conclusion  Patients with younger age, preoperative hypocalcemia, higher preoperative ALP, and higher preoperative PTH level are more likely to develop severe hypocalcemia after TPTX+AT or TPTX.