The aims of our systematic review were to quantify the expected rate of procedural success, early and late complications during CIED implantation using US-guided puncture of the axillary vein and to perform a meta-analysis of those studies that compared the US technique (intervention) versus conventional techniques (control) in terms of complication rates. MEDLINE, ISI Web of Science, and EMBASE were searched for eligible studies. Pooled Odds Ratio (OR) and Pooled Mean Difference (PMD) for each predictor were calculated. The quality of evidence (QOE) was evaluated according to the GRADE guidelines. Thirteen studies were included a total of 2073 patients. The overall success of US-guided venipuncture for CIED implantation was 96.8%. As regards early complications, pneumothorax occurred in 0.19%, arterial puncture in 0.63%, and severe hematoma/bleeding requiring intervention in 1.1%. No cases of hemothorax, brachial plexus, or phrenic nerve injury were reported. As regards late complications, the incidence of pocket infection, venous thromboembolism, and leads dislodgement was respectively 0.4%, 0.8%, and 1.2%. In the meta-analysis (five studies), the intervention group (US-guided venipuncture) had a trend versus a lower likelihood of having a pneumothorax (0.19% vs 0.75%, p = 0.21), pocket hematoma (0.8% vs 1.7%, p = 0.32), infection (0.28% vs 1.05%, p = 0.29) than the control group, but this did not reach statistical significance. The overall QOE was low or very low. In conclusions we found that the US-guided axillary venipuncture for CIEDs implantation was associated with a low incidence of early and late complications and a steep learning curve.