Background: Pruritus is a distressing symptom of systemic opioid analgesia that responds poorly to conventional antipruritus treatments. This study aimed to determine the incidence and risk factors for postoperative pruritus using intravenous patient-controlled analgesia (IV-PCA). Methods: Opioid-naïve patients who underwent morphine-based IV-PCA for postoperative pain at a tertiary center between January 1, 2020, and June 30, 2023, were included retrospectively. The primary outcome was pruritus within 72 h after surgery. Cumulative morphine consumption and pain numerical rating scores were measured to evaluate the potential impact of pruritus on postoperative pain control. Results: A total of 1,696 patients were enrolled, of whom 119 (7.0%) developed pruritus during the study period. Five independent factors for pruritus were identified, including intraoperative uses of hydroxyethyl starch solutions [adjusted odds ratio (aOR): 0.13, 95% confidence interval (CI): 0.04–0.43], lockout interval of IV-PCA (aOR: 0.50, 95% CI: 0.27–0.94, on base-2 logarithmic scale), droperidol addition to morphine solutions (aOR: 0.53, 95% CI: 0.35–0.81), cumulative morphine dose (aOR: 1.76, 95% CI: 1.47–2.12, on base-2 logarithmic scale), and postoperative uses of antihistamines (aOR: 2.90, 95% CI: 1.83–4.60) (c-statistic = 0.745). Patients with pruritus had higher postoperative morphine consumption (median: 67.5 mg, interquartile range: 38.3–94.0 vs. 38.0 mg, 21.0–65.4, p<0.0001) but similar pain intensity compared to those without pruritus. Conclusion: Increasing the lockout interval and the droperidol regimen may protect patients from morphine-induced pruritus after IV-PCA. Further studies are warranted to clarify the mechanisms underlying the anti-pruritus effects of hydroxyethyl starch.