In addition to hypocalcemia, patients with hypoparathyroidism report poor quality of life (QOL), complaining of fatigue and “brain fog.” Parathyroid hormone (PTH) therapy can effectively manage hypocalcemia;​ however, the effects of PTH treatment on QOL are unclear. Thirty-one patients with hypoparathyroidism were treated in an open-label study with full replacement subcutaneous PTH 1-34 twice daily for up to 5.3 years, with individualized fine-dosing titration. Prior to initiation of PTH 1-34, conventional therapy was optimized. The 36-Item Short Form (SF-36) Health Survey, Fatigue Symptom Inventory (FSI), and 6-minute walk test (6MWT) were assessed at PTH start (baseline), every 6 months on PTH, and after PTH discontinuation. The SF-36 assesses physical function (PF), physical role limitations (RP), bodily pain (BP), general health (GH), vitality (VT), emotional role limitations (RE), social function (SF), and mental health (MH). Compared to population norms, patients at baseline had lower scores in RP, GH, VT, and MH (p < 0.05), consistent with impaired QOL. With PTH therapy, only GH at 6 months and VT at 12 months improved (p < 0.05). At the last treatment time point, RP, VT, and SF improved compared to baseline (p < 0.05). However, follow-up scores were unchanged from baseline or last PTH treatment, except for SF, which had decreased at follow-up compared to on-PTH (p < 0.05). On the FSI, there were no changes in fatigue frequency;​ perceived interference was improved at 12 and 18 months and composite severity was improved only at 60 months (p < 0.05). The 6MWT measures did not change. In conclusion, hypoparathyroidism is associated with decreased QOL. Despite the bias in open-label studies to predict improvements in QOL, PTH therapy had limited and non-sustained effects on QOL, inconclusive changes in fatigue experience, and no change in the 6MWT. Although PTH 1-34 can adequately manage the hypocalcemia in hypoparathyroidism, its effects on QOL appear to be minimal.