Background <p>Perioperative dexmedetomidine is reported to reduce complications and even in-hospital mortality after cardiac surgery. We therefore tested the hypothesis that perioperative dexmedetomidine may improve long-term outcomes after cardiac surgery.</p> Methods <p>This was long-term follow-up of a randomized trial. We enrolled 285 patients aged 60&#xa0;years or older who were scheduled for elective cardiac surgery. Patients were randomized to receive either dexmedetomidine or placebo (normal saline) during and early after surgery. Follow-up was conducted for up to 6&#xa0;years post-surgery. The primary endpoint was overall survival. Secondary outcomes included major adverse cardiovascular events (MACE)-free and hospital-free survivals, as well as cognitive function and quality of life in 6-year survivors.</p> Results <p>All 285 patients were included in final analysis. Median follow-up duration was 80&#xa0;months (interquartile range 30 to 80). Overall survival did not differ between the two groups: there were 18 deaths (12.6%) with placebo versus 22 deaths (15.5%) with dexmedetomidine; hazard ratio (HR) 1.22, 95% CI 0.65 to 2.27, <i>p</i> = 0.418. MACE-free survival was 23 (16.1%) with placebo versus 24 (16.9%) with dexmedetomidine; HR 1.03, 95% CI 0.58 to 1.83, <i>P</i> = 0.911. Hospital-free survival was 39 (27.3%) with placebo versus 42 (29.6%) with dexmedetomidine; HR 1.04, 95% CI 0.67 to 1.61, <i>P</i> = 0.853. Among 6-year survivors, the scores of cognitive function and quality of life were similar between groups.</p> Conclusions <p>We found that, for older patients undergoing elective cardiac surgery, dexmedetomidine administered during and early after surgery did not alter overall and MACE-free survivals, as well as long-term cognitive function and quality of life. However, considering the underpowered sample size and non-negligible loss to follow-up rate, our results need further confirmation.</p> Trial registration <p>ClinicalTrials.gov: NCT03289325 (September 20, 2017).</p>