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Supplemental Digital Content is available in the text Objectives: The aim was to compare the long-term outcomes of low-dose dexmedetomidine versus placebo in a randomized controlled trial (ChiCTR-TRC-10000802). Background: Low-dose dexmedetomidine infusion decreased delirium occurrence within 1 week after surgery in elderly admitted to the intensive care unit (ICU) after noncardiac surgery, but the long-term outcome of this intervention is unknown. Methods: Patients or their family members were telephone-interviewed for a 3-year follow-up data collection of survival, cognitive function assessed with the modified Telephone Interview for Cognitive Status, and quality of life evaluated with the World Health Organization Quality of Life. Results: Of the 700 patients, 23 (3.3%) were lost at 3-year follow-up. The 3-year overall survival was not statistically different between the dexmedetomidine and placebo groups [114 deaths vs 122/350; hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.68–1.13, P = 0.303]. The survival rates at 6 months, 1 year, and 2 years were significantly higher in the dexmedetomidine than in the placebo group (rate difference of 5.2%, 5.3%, and 6.7% respectively; all P < 0.05). The remaining 98.4% (434/441) 3-year survivors, the dexmedetomidine group, had significantly better cognitive function (mean difference 4.7, 95% CI 3.8–5.6, P < 0.0001) and quality of life (physical domain: 13.6 [10.6–16.6]; psychological domain: 15.2 [12.5–18.0]; social relationship domain: 8.1 [5.5–10.7]; environment domain: 13.3 [10.9–15.7]; all P < 0.0001) than in the placebo group. Conclusions: For elderly admitted to ICU after noncardiac surgery, low-dose dexmedetomidine infusion did not significantly change 3-year overall survival, but increased survival up to 2 years, and improved cognitive function and quality of life in 3-year survivors. [ABSTRACT FROM AUTHOR]