Objective: Fentanyl-induced cough (FIC) is a common complication with a reported incidence from 18.0% to 74.4% during general anesthesia induction. FIC increases the intrathoracic pressure and risks of postoperative nausea and vomiting, yet available treatments are limited. This study was designed to investigate whether administering fentanyl via a slow intravenous fluid line can effectively alleviate FIC during induction of total intravenous general anesthesia., Methods: A total number of 1200 patients, aged 18-64 years, were enrolled, all of whom were American Society of Anesthesiologists (ASA) grade I or II undergoing scheduled surgeries. All patients received total intravenous general anesthesia, which was induced sequentially by midazolam, fentanyl, propofol, and cisatracurium injection. Patients were randomly assigned to receive fentanyl 3.5 μg/kg via direct injection (control group) or via a slow intravenous fluid line. FIC incidence and the severity grades were analyzed with the Mann-Whitney test. Other adverse reactions, such as hypotension, hypertension, bradycardia, tachycardia, hypoxemia, vomiting, and aspiration, during induction were also observed. The online clinical registration number of this study was ChiCTR-IOR-16009025., Results: Compared with the control group, the incidence of FIC was significantly lower in the slow intravenous fluid line group during induction (9.1%, 95% confidence interval (CI): 6.7%-11.4% vs. 55.9%, 95% CI: 51.8%-60.0%, P=0.000), as were the severity grades (P=0.000). There were no statistical differences between the two groups with regard to other adverse reactions (P>0.05)., Conclusions: The administration of fentanyl via a slow intravenous fluid line can alleviate FIC and its severity during induction for total intravenous general anesthesia. This method is simple, safe, and reliable, and deserves clinical expansion.