Aims Recurrence of secondary hyperparathyroidism (SHPT) remains a big challenge in uremic patients who underwent total parathyroidectomy with auto-transplantation (tPTX-AT). However, the relationship between perioperative intervention and recurrence of SHPT remains unclear. Dexmedetomidine has been used safely and effectively in uremic patients’ anesthesia. The aim of the study was to explore the effect of dexmedetomidine on the recurrence of SHPT and speculate the possible mechanism of action. Methods Records of patients who underwent tPTX-AT between 2017 and 2018 were retrospectively analyzed. The study consisted of patients who received dexmedetomidine intra-operatively and the controls were patients who did not receive dexmedetomidine. The primary endpoint was the difference in the recurrence of SHPT one year after surgery between the two groups. The secondary endpoint was health-related quality of life scores. Analysis included propensity score matching and multivariable logistic regression. Results Of 354 patients, 133 had received dexmedetomidine intraoperatively, and the total recurrence rate of SHPT was 10.2%. After propensity score matching, patients who received dexmedetomidine had a 3.80-fold decreased risk of SHPT recurrence (odds ratio, 0.263; 95% confidence interval, 0.081 to 0.854; P=0.026) and exhibited a better quality of life in terms of physical functioning and general health, and less emotional role limitations compared with those in control group. Conclusion In uremic patients who received tPTX-AT, there was an association between dexmedetomidine use and decreased risk of SHPT recurrence. However, further studies are needed to accurately assess the effects and mechanism of action of dexmedetomidine on the prognosis of this population.