Background The current available literature is not unanimous in reporting the utility of short-axis and long-axis techniques for radial artery cannulation in both adults and children. This study was designed to compare short-axis out-of-plane (SA-OOP) and long-axis in-plane (LA-IP) techniques in ultrasound-guided radial artery cannulation in adults. Methods In this prospective randomized controlled trial, 150 adult patients of American Society of Anesthesiologists physical status I–III aged between 18 and 70 years were included. All patients were randomized into two groups (group SA-OOP) and (group LA-IP) of 75 each undergoing ultrasound-guided radial artery cannulation. The primary outcome was successful cannulation in the first attempt. Secondary outcomes included antero-posterior arterial diameter, skin-to-artery distance, ultrasonic localization time, cannulation time, no of attempts to cannulate artery, cannula insertion failure, and vascular complications. Results First-attempt arterial cannulation was successful in 80 % of patients in the SA-OOP group as opposed to 82.6 % patients in the LA-IP group ( p  = 0.67). The time to cannulate the artery was similar between the two groups, but the time to localize artery was significantly higher in the long-axis technique ( p  < 0.001). Conclusions The first-attempt cannulation success rate and cannulation time in adult patients are similar in ultrasound-guided radial artery cannulation with both short-axis as well as long-axis techniques. Trial registration Clinical Trial Registry of India (CTRI/2015/02/005552).