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Background and Aims Intra-pocket ultrasound-guided axillary vein puncture (IPUS-AVP) for venous access in implantation of transvenous cardiac implantable electronic devices (CIED) is uncommon due to the lack of clinical evidence supporting this technique. This study investigated the efficacy and early complications of IPUS-AVP compared to the standard method using cephalic vein cutdown (CVC) for CIED implantation. Methods ACCESS was an investigator-led, interventional, randomized (1:1 ratio), monocentric, controlled superiority trial. A total of 200 patients undergoing CIED implantation were randomized to IPUS-AVP (n = 101) or CVC (n = 99) as a first assigned route. The primary endpoint was the success rate of insertion of all leads using the first assigned venous access technique. The secondary endpoints were time to venous access, total procedure duration, fluoroscopy time, X-ray exposure, and complications. Complications were monitored during a follow-up period of three months after procedure. Results IPUS-AVP was significantly superior to CVC for the primary endpoint with 100 (99.0%) vs. 86 (86.9%) procedural successes (P =.001). Cephalic vein cutdown followed by subclavian vein puncture was successful in a total of 95 (96.0%) patients, P =.21 vs. IPUS-AVP. All secondary endpoints were also significantly improved in the IPUS-AVP group with reduction in time to venous access [3.4 vs. 10.6 min, geometric mean ratio (GMR) 0.32 (95% confidence interval, CI, 0.28–0.36), P <.001], total procedure duration [33.8 vs. 46.9 min, GMR 0.72 (95% CI 0.67–0.78), P <.001], fluoroscopy time [2.4 vs. 3.3 min, GMR 0.74 (95% CI 0.63–0.86), P <.001], and X-ray exposure [1083 vs. 1423 mGy.cm², GMR 0.76 (95% CI 0.62–0.93), P =.009]. There was no significant difference in complication rates between groups (P =.68). Conclusions IPUS-AVP is superior to CVC in terms of success rate, time to venous access, procedure duration, and radiation exposure. Complication rates were similar between the two groups. Intra-pocket ultrasound-guided axillary vein puncture should be a recommended venous access technique for CIED implantation. [ABSTRACT FROM AUTHOR]