Abstract Background and aims The use of ultrasound (US)-guided venous puncture for cardiac pacing/defibrillation lead placement may minimize the risk of peri-procedural complications and radiation exposure. However, none of the published studies have been sufficiently powered to recommend this approach as the standard of care. We compare the safety and efficacy of ultrasound-guided axillary venous puncture (US-AVP) versus fluoroscopy-guided access for cardiac implantable electronic devices (CIED) by performing an individual patient data meta-analysis based on previously published studies. Methods We conducted a thorough literature search encompassing longitudinal investigations (five randomized and one prospective studies) reporting data on Xray-guided and US-AVP for CIED procedures. The primary endpoint was to compare the safety of the two techniques. Secondary endpoints included the success rate of each technique, the necessity of switching to alternative methods, the time needed to obtain venous access, Xray exposure and the occurrence of peri-procedural complications. Results Six longitudinal eligible studies were identified including 700 patients (mean age 74.9 ±12.1 years, 68.4% males). The two approaches for venous cannulation showed a similar success rate. The use of a Xray guided approach significantly increased the risk of inadvertent arterial punctures (OR: 2.15, 95% CI: 2.10-2.21, p=0.003), after adjustment for potential confounders. Conversely, an US-AVP approach reduces time to vascular access, radiation exposure and the number of attempts to vascular access. Conclusions The US-AVP enhances safety by reducing radiation exposure and time to vascular access while maintaining a low rate of major complications compared to the x-ray-guided approach.