Objective To summarize the occurrence of operative failures after microwave ablation (MWA) in patients with primary hyperparathyroidism (pHPT), analyze the possible reasons, and explore strategies for preventing and managing these situations. Methods This retrospective study reviewed 91 pHPT patients who underwent MWA from April 2015 to November 2019. A cure was defined as the reestablishment of normal calcium homeostasis lasting a minimum of 6 months. An operative failure was defined as a failure to normalize serum intact parathyroid hormone (iPTH) and/or calcium levels at 6 months or longer. Patients who encountered operative failures were compared with patients who were successfully cured. Results Eighty-eight pHPT patients, consisting of 29 men and 59 women, were finally enrolled. The median follow-up duration was 15.9 months (IQR, 6.1-31.5 months). Seventy-eight patients (78/88, 88.6%) were cured. Ten (10/88, 11.4%) patients experienced operative failure, including 9 persistent pHPT (10.2%) and 1 (1.1%) recurrent pHPT. Small parathyroid nodules (maximum diameter < 0.6 cm) and incomplete ablation were the two key factors leading to operative failure. Of the 9 patients with a maximum nodule diameter less than 0.6 cm, 77.8% (7/9) of them encountered operative failure. Conclusion Operative failure occurred in 11.4% of the pHPT patients who underwent MWA. The possibility of operative failure was increased when the maximum diameter of parathyroid nodule was less than 0.6 cm. Complete ablation could help avoid operative failure.