Context: Conventional therapy for hypoparathyroidism aims to alleviate symptoms of hypocalcemia but does not address insufficient parathyroid hormone (PTH) levels. Objective: Assess the long-term efficacy and safety of TransCon PTH (palopegteriparatide) for hypoparathyroidism. Design: Phase 3 trial with a 26-week, double-blind, placebo-controlled period followed by a 156-week, open-label extension (OLE). Setting: Twenty-one sites across North America and Europe. Participants: A total of 82 adults with hypoparathyroidism were randomized and received study drug and 78 completed week 52. Intervention(s): All OLE participants received TransCon PTH administered once daily. Main Outcome Measure(s): Multicomponent efficacy endpoint: proportion of participants at week 52 who achieved normal serum calcium (8.3-10.6 mg/dL) and independence from conventional therapy (≤600 mg/day of elemental calcium and no active vitamin D). Other efficacy endpoints included patient-reported outcomes and bone mineral density. Safety was assessed by 24-hour urine calcium and treatment-emergent adverse events. Results: At week 52, 81% (63/78) met the multicomponent efficacy endpoint, 95% (74/78) achieved independence from conventional therapy, and none required active vitamin D. Patient-reported outcomes showed sustained improvements in quality of life, physical functioning, and well-being. Mean bone mineral density Z-scores decreased toward age- and sex-matched norms from baseline to week 52. Mean (SD) 24-hour urine calcium excretion decreased from 376 (168) mg/day at baseline to 195 (114) mg/day at week 52. Most treatment-emergent adverse events were mild or moderate and none led to trial discontinuation during the OLE. Conclusion: At week 52 of the PaTHway trial, TransCon PTH showed sustained efficacy, safety, and tolerability in adults with hypoparathyroidism.