Arterial puncture, for obtaining an analysis of blood gas, is an interventional procedure often performed in emergency departments and intensive care units. This study compares the ultrasound (US) guided method with the conventional digital palpation method in radial artery puncture (RAP) for blood gas analysis in septic shock patients. This is a prospective, single-centre study. Septic shock patients over 18 years of age who needed a RAP sample for blood gas analysis were included. Patients with local infection or trauma at the puncture site, arteriovenous fistula, vascular graft, coagulopathy, a positive Allen test, or did not want to participate were excluded. Patients were randomized into two groups and RAP was obtained with either the US-guided method or the conventional method. The main outcomes were success at first entry, the number of attempts before success, and the time to success. The 50 eligible patients were randomized into two groups. First entry success rate for the US-guided group and the conventional group was 80% and 42%, respectively. The number of attempts before success and time to success was significantly higher in the conventional group. The US-guided method has been found to be more successful in terms of first entry success, the number of attempts before success, and the time to success when compared to the conventional method.