OBJECTIVE To report the incidence of adverse events during euthanasia of client-owned dogs administered either intravenous pentobarbital/phenytoin (PP) or PP after propofol delivery. METHODS Prospective, observational, multi-site study. METHODS Four hundred thirty-six dogs undergoing client-elected euthanasia over a 1-year period. METHODS Interventions included placement of an IV catheter and delivery of euthanasia agents (PP for the PP group, propofol followed by PP for the propofol group). Seven pre-determined adverse events were recorded: agonal breaths, urination, defecation, vocalization, muscle activity, dysphoria, and catheter complications. Euthanasia scores for each patient were defined as the sum of all adverse events (0-7) the patient exhibited. RESULTS Two hundred thirty-six dogs were in the PP group and 200 dogs were in the propofol group. No significant differences were detected in the dose of PP administered (166.9 ± 105.6 mg/kg for PP group, 182.6 ± 109.8 mg/kg for propofol group). Propofol dogs received 4.5 ± 2.9 mg/kg propofol. The incidence of ≥ 1 adverse event was 35.2% in the PP group and 26.5% in the propofol group (P = 0.052). Mean euthanasia scores (0.47 PP group, 0.32 propofol group) were not significantly different (P = 0.08). Propofol significantly reduced the incidence of muscle activity (6% vs. 14%, odds ratio 0.39; P = 0.0079). CONCLUSIONS There was no difference in the likelihood of the studied adverse events during client-elected euthanasia in dogs when propofol was used prior to PP. There was a significant reduction in perimortem muscle activity if propofol was given prior to PP.