Background and Aims Parathyroidectomy (PTX) is an effective method for the treatment of refractory or progressive secondary hyperparathyroidism (SHPT). Severe hypocalcemia (SH) is a common and serious postoperative complication. Preoperative prediction of SH has crucial clinical value for postoperative management and targeted intervention of SHPT patients, but the risk prediction scoring model has not been established. Therefore, this study was designed to investigate SH risk factors in patients with SHPT after PTX and construct a preoperative risk prediction score model for clinical application.Methods The clinical data of 513 patients with SHPT who underwent total PTX plus autotransplantation in the 960th Hospital of PLA from November 2010 to March 2022 were retrospectively analyzed. According to admission time, they were allocated to model group (404 cases) and validation group (109 cases). The patients were classified into SH and non-SH groups according to the lowest serum calcium level within 3 d after surgery. Univariate and multivariate analyses were conducted to determine the independent risk factors for postoperative SH. Logistic regression was used to establish a predictive scoring model. The receiver operating characteristic curve (ROC) was applied to verify the model internally and externally in the model and validation groups, respectively.Results In the whole group of 513 patients, SH occurred in 237 cases (46.20%). In the model group, univariate analysis showed that pruritus, height shortening, age, preoperative hemoglobin, alkaline phosphatase (ALP), albumin, serum calcium, intact parathyroid hormone (iPTH), osteocalcin, β-Crosslaps (β-CTX) were significantly associated with postoperative SH (all P<0.05). Multivariate analysis showed that preoperative ALP>363.5 U/L, iPTH>2 239 pg/mL, β-CTX>3.305 μg/L, and height shortening were independent risk factors for postoperative SH and preoperative serum calcium>2.50 mmol/L were protective factor against postoperative SH (all P<0.05). The ALP>363.5 U/L, iPTH>2 239 pg/mL, and β-CTX>3.305 μg/L were used to establish the SH risk prediction scoring model, with the positive corresponding points of 7, 4, and 6, respectively, and the negative value of 0. The results showed that the incidence of SH was 58.82% at 10-13 points and 82.93% at 17 points. The area under ROC curves for the model group and the validation group was 0.811 (95% CI=0.768-0.853) and 0.826 (95% CI=0.745-0.906), respectively, both of which were statistically significant (both P<0.05).Conclusion The risk prediction scoring model effectively predicts the incidence of SH after PTX in SHPT patients, which can be used to identify high-risk patients before operation and provide an essential reference for clinical guidance of postoperative management and treatment of SHPT patients.