Our aim was to identify potential risk factors associated with severe hypocalcemia (SH) after microwave ablation (MWA) in patients with secondary hyperparathyroidism (SHPT). This retrospective cross‐sectional study enrolled 204 consecutive patients (with 387 parathyroid glands) who underwent MWA between July 2015 and May 2018. Clinical parameters, laboratory indices, and parathyroid gland characteristics were analyzed to assess risk factors associated with SH after MWA. SH was defined as serum calcium level lower than 1.875 mmol/L (7.5 mg/dL) after MWA. Two models (I and II) for pre‐MWA and post‐MWA prediction were established, respectively. In accordance with the KDIGO guidelines, the target value for intact parathyroid hormone (iPTH) less than 300 pg/mL within 7 days after MWA was considered as a successful procedure. The success rate of MWA was 71.6% (146/204). The incidence of hypocalcemia and SH after MWA was 35.8% and 22.06%, respectively. The pre‐MWA prediction models I and II showed that high pre‐MWA iPTH, a dramatic reduction in iPTH, low pre‐MWA serum calcium, multiple ablated gland, and lack of pruritus symptoms were risk factors for developing SH. The accuracy (82.23% versus 83.25% in models I and II, respectively), sensitivity (34.88% versus 44.19%), specificity (95.45% versus 94.59%), positive predictive value (PPV) (68.18% versus 70.37%), and negative predictive value (NPV) (84% versus 85.37%) of both models were promising. The logistic regression fitting of the nomograms showed high prediction efficiency (0.845 and 0.863). High pre‐MWA iPTH, dramatic reductions in iPTH, low pre‐MWA serum calcium, multiple gland ablation, and no pruritus symptoms were predictors of SH.