Objective: The objective of the study was to compare landmark-based and ultrasound-guided techniques of central venous catheter insertion (CVC). Design: Randomized controlled trial (2021---2023). Setting: Zagazig University Hospitals (ZUH), a tertiary care center. Patients: Adult patients in whom CVC insertion is indicated. Main variables of interest: Demographic and clinical peri-procedural data, the safety of the technique, time of performance, and cost-effectiveness were compared. Results: Patient ages ranged from 17 to 80 years with 56% being males. Urgent indications were found in around 22% without significant differences between groups. Regarding the time of performance, the ultrasound-guided method had slightly but significantly less time of perfor- mance (25.7 ± 4.3; range: 18−33) compared to the blind technique (26.9 ± 7.4; range: 15−45) (P-value < 0.001) with a higher but non-significant number of patients without complications (64% vs 52%; P-value = 0.2). Failure to insert the CVC into the IJV occurred in 12 patients (12%) with the blind technique and in eight patients (8%) with the ultrasound-guided technique (P- value = 0.04). Carotid artery puncture with neck hematoma occurred in only 8 (8%) patients with the blind technique (P-value = 0.04). Excess cost was consumed in only 36 patients (36%) in the blind technique group (P-value = 0.001). Conclusion: Point-of-care ultrasonography bundle for CVC insertion is considered superior to, safer, and more cost-effective than the blind technique.