Background <p>Supraventricular tachycardia affects many critically ill patients. Dexmedetomidine, a commonly used sedative, has sympatholytic and vagotonic effects that may alter atrioventricular nodal conduction and contribute to SVT. We aim to determine the association between dexmedetomidine exposure and clinically significant supraventricular tachycardia in a heterogeneous cohort of mechanically ventilated, critically ill adults.</p> Methods <p>This retrospective cohort study included critically ill patients from 11 hospitals admitted between July 2018 and October 2022, who were intubated within 48&#xa0;h of admission. The primary exposure was intravenous dexmedetomidine. The primary outcome was occurrence of clinically significant supraventricular tachycardia, defined as heart rate &gt; 100 beats per minute and administration of intravenous antiarrhythmic drugs. Time-dependent propensity score matching was used to account for time-varying exposures and confounders.</p> Results <p>7,276 patients with dexmedetomidine exposure were matched to 7,276 patients without dexmedetomidine exposure. Clinically significant supraventricular tachycardia occurred more frequently at 7 days in the dexmedetomidine group (<i>n</i> = 1,616, 22.2%) compared to matched controls (<i>n</i> = 1,186, 16.3%, absolute risk difference 5.73%, <i>p</i> &lt; 0.05). After accounting for competing risks, dexmedetomidine use remained associated with a higher risk of supraventricular tachycardia (<i>p</i> &lt; 0.05).</p> Conclusions <p>Dexmedetomidine exposure is associated with clinically significant supraventricular tachycardia in critically ill, mechanically ventilated patients.</p>