Purpose <p>Cardiac arrest due to a sharp increase in serum potassium one minute after reperfusion in liver transplantation (LT) is fatal. We sought to compare prophylactic nebulized salbutamol versus glucose-insulin for decreasing potassium during reperfusion and to guide the selection of potassium reduction strategies in LT.</p> Methods <p>We conducted a randomized, double-blind trial, enrolled patients undergoing LT with preoperative baseline serum potassium levels ≥ 4&#xa0;mmol/L. Patients were randomized into two groups to receive either glucose-insulin (Group A) or nebulized salbutamol (Group B) as preventive potassium reduction regimens. The primary outcome was the incidence of hyperkalemia (defined as serum potassium &gt; 5.5&#xa0;mmol/L) 30&#xa0;s after reperfusion (Rep1).</p> Results <p>One hundred participants were included in the analysis. The incidence of hyperkalemia at Rep1 was significantly lower in Group B than in Group A (36% vs. 56%, <i>P</i> = 0.045). Following administration and prior to reperfusion, the lowest potassium levels were achieved at 30&#xa0;min in Group A and 45&#xa0;min in Group B, respectively. The maximum decrease in the serum potassium level was significantly greater in Group B (<i>P</i> &lt; 0.001). No significant differences in the incidence of postreperfusion syndrome were observed between the groups. Surprisingly, Group B had milder blood glucose fluctuations, higher heart rate and mean arterial pressure, lower driving pressure, and lower incidence of postoperative atelectasis.</p> Conclusion <p>Nebulized salbutamol is superior to glucose-insulin for preventing acute hyperkalemia during the reperfusion period and may benefit patients undergoing LT.</p> Clinical trial notation <p>Trial registration no. NCT05589441 ClinicalTrials.gov.</p>