Objective Hypoparathyroidism is a common complication after thyroidectomy. It is not yet possible to predict in which patients hypoparathyroidism will persist. We aim to determine whether a decrease in PTH levels, measured at the first postoperative day, can identify patients with a high risk for persistent hypoparathyroidism one year after thyroidectomy. Design Prospective multi-center cohort study. Methods Patients undergoing total or completion thyroidectomy were included. We measured PTH levels preoperatively and on the first postoperative day. Primary outcome is the proportion of patients with persistent hypoparathyroidism, defined as the need for calcium supplementation one year after surgery. Results We included 110 patients of which 81 were used for analysis of the primary outcome. At discharge 72.8% of patients were treated with calcium supplementation. Persistent hypoparathyroidism was present in 14 patients (17.3%) at one-year follow-up, all of them had a decrease in PTH >70% at the first postoperative day. These 14 were 43.8% of the 32 patients who had such a decrease. In the group of 49 patients (59.8%) without a PTH >70% decrease, none had persistent hypoparathyroidism one year after surgery (P-value <0.001). A decrease of >70% in PTH levels had a sensitivity of 100.0% (95% CI: 85.8–100.0%), a specificity of 73.1% (95% CI: 62.5–83.7%) and an area under the curve of 0.87 (95% CI: 0.79–0.94) to predict the risk for persistent hypoparathyroidism. Conclusion In our study a decrease in PTH levels of >70% after total or completion thyroidectomy is a reliable predictor for persistent hypoparathyroidism, and this should be confirmed in larger cohorts.