Objective: To compare first attempt success rate for ultrasound-guided (USG) versus direct palpation (DP) for radial, femoral, and dorsalis pedis artery cannulations in adult intensive care unit (ICU) patients. Design: Prospective randomized clinical trial. Setting: Mixed adult ICU of a University Hospital. Participants: Adult patients (& GE;18 years) admitted to the ICU requiring invasive arterial pressure monitoring were included. Exclusion criteria were patients with a pre-existing arterial line and cannulated with other than a 20-gauge cannula for radial and dorsalis pedis artery. Intervention: Comparison of arterial cannulation by USG versus palpation technique in radial, femoral and dorsalis pedis arteries. Main variables of interest: Primary outcome was first attempt success rate, secondary out-comes were assessing time for cannulations, number of attempts, overall success rate, complications, and comparison of two techniques on patients requiring vasopressor. Results: 201 patients were enrolled in study, with 99 randomized to DP group and 102 to USG group. Arteries (radial, dorsalis pedis, femoral) cannulated in both groups were comparable (P = .193). Arterial line was placed on first attempt in 85 (83.3%) in USG group versus 55 (55.6%) in DP group (P = .02). Cannulation time in USG group was significantly shorter compared to DP group. Conclusions: In our study, USG arterial cannulation, compared to palpatory technique, had a higher success rate at first attempt and a shorter cannulation time. Clinical Trial Registry of India number: CTRI/2020/01/022989. & COPY; 2023 Published by Elsevier Espana, S.L.U.