Objective: To test the hypothesis that pain at the site of peripheral intravenous infusion is greater if potassium chloride is administered in sterile water than if it is administered in saline. Methods: A randomized, double-blind study of infusion-site pain was completed with 36 hospital inpatients with hypokalemia who required 1, 2, or 3 peripheral intravenous infusions of potassium chloride (10 mmol) in 100 mL of IV fluid. Patients were randomly assigned to 1 of 3 groups and were administered potassium chloride in 1 of 3 infusion fluids: sterile water, 0.9% sodium chloride, or 0.45% sodium chloride. Patients rated the degree of pain at the injection site using a 10-point numeric rating scale before the start, at 15 min after the start, and at the end of each of the 3 infusions. Results: Baseline mean pain scores were similar for all groups. Pain scores in the sterile water group at the end of first, second, and third infusions were significantly higher than those in the 0.9% sodium chloride group (p = 0.003, p = 0.003, p = 0.043, respectively), and were also significantly higher than those in the 0.45% sodium chloride group at the end of first and second infusions only (p = 0.003, p = 0.007, respectively) There were no significant differences between the 0.9% and 0.45% sodium chloride groups. Conclusion: Peripheral intravenous infusion of potassium chloride produces significantly more pain at the infusion site when administered in sterile water than in saline.