ImportanceDefinitive treatment of primary hyperparathyroidism (pHPT) with curative parathyroidectomy has been shown to improve nonspecific neurocognitive symptoms and may improve long-term quality of life (QOL). However, QOL is not currently routinely assessed preoperatively, and as a result, diminished QOL may be overlooked as an indication for surgery.ObjectiveTo examine results for measures of long-term QOL after parathyroidectomy in patients with pHPT.Evidence ReviewA systematic, English-language literature review was performed to assess the long-term association of parathyroidectomy, defined as a minimum of 1-year postoperative follow-up, with QOL in patients with pHPT. We conducted a search of PubMed and Scopus using Medical Subject Heading (MeSH) terms for hyperparathyroidism, parathyroid hormone, parathyroidectomy, hypercalcemia, and quality of life. All relevant literature published between June 1998 and February 15, 2021, was included. Study selection was guided by the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) strategy.FindingsThirty-one studies conducted in 14 countries with a minimum of 1 year of follow-up were included, comprising 3298 patients with pHPT (2975 underwent parathyroidectomy; 323 were observed), 5445 age- and sex-matched control participants, and 386 control patients with benign thyroid disease. To assess QOL, 21 studies (68%) used a general tool, the 36-item Short Form Survey (SF-36), and 8 (26%) used the disease-specific tool Parathyroidectomy Assessment of Symptoms (PAS). The remaining studies used a combination of 10 additional QOL tools. The median follow-up period was 1 year (range, 1-10 years). Of the 31 studies, 27 (87%) demonstrated significant score improvement in long-term QOL after parathyroidectomy, including 1 study that showed continued improvement in QOL 10 years after parathyroidectomy. The remaining 4 studies (13%) reported mixed results.Conclusions and RelevanceThis systematic review suggests that parathyroidectomy is associated with improved and sustained QOL in patients with pHPT. Patients with pHPT should be screened with a validated QOL tool such as the SF-36 or PAS at the time of diagnosis to guide discussion of these symptoms in the preoperative setting and the potential for long-term improvement after curative parathyroidectomy.