Introduction: Dexmedetomidine is frequently used as a sedative in the pediatric intensive care unit (PICU) despite limited data on the risk factors, manifestations, and treatment of withdrawal. Clonidine is often utilized to treat withdrawal based on mechanism of action, but data showing efficacy is lacking. We hypothesized that patients treated with clonidine would have less agitation, hypertension, and tachycardia. Methods: This retrospective observational cohort study took place in a 30-bed PICU over a two year period. Data was collected on all intubated patients receiving dexmedetomidine infusions except patients on clonidine prior to admission and those receiving end of life comfort care. Variables of interest collected via electronic medical record included maximum infusion rate, days on infusion, infusion wean duration, exposure to other sedatives, treatment with clonidine during weaning, Withdrawal Assessment Tool 1 (WAT-1) scores, heart rate and blood pressure changes from pre-wean baseline, and presence of agitation, as measured by Richmond Agitation Sedation Score greater than 0. Variables were compared with non-parametric tests (all data median [IQR]). Results: While there was a significant difference in the maximum infusion rates of dexmedetomidine in the clonidine group (n=17, 1.6 mcg/kg/hr [1.2-2.0]) compared to the no clonidine group (n=13, 1.0 mcg/kg/hr [0.8-1.4]; p= 0.01), there was no significant difference in days on infusion (9.0 [7.0-11.0] vs. 5.0 [5.0-11.5]; p= 0.17) or infusion wean duration (1.0 [1.0-2.0] vs. 1.0 [1.0-2.5] days; p= 0.87). There was no difference in presence of agitation (8 [47%] vs. 7 [54%], p= 0.71), presence of delirium (6 [35%] vs. 5 [39%]; p= 0.93), WAT-1 scores greater than 3 (8 [47%] vs. 7 [54%]; p= 0.70), a heart rate elevation >15 bpm (14 [82%] vs. 10 [77%]; p= 1.0), or at least two episodes of a systolic blood pressure increase above 10 mmHg over baseline (10 [59%] vs. 11 [85%]; p= 0.23) in the first 24 hours post infusion. Conclusions: In this small cohort of patients treated with prolonged dexmedetomidine infusions, clonidine administration was not associated with reduced agitation, WAT-1 scores, or heart rate and/or blood pressure changes post infusion.