Background: Although ultrasound guidance for axillary vein (AV) access (USGAVA) has been described as a reliable technique for cardiac implantable electronic device (CIED) implantation, no data is available on the use of handheld ultrasound devices (HUD) in such a setting. Objective: We investigated the feasibility of using a HUD for USGAVA in patients referred to our Institution for CIED implantation. Methods: The procedure details of 80 consecutive patients undergoing USGAVA (Group-1) from June 2020 to June 2021 were prospectively collected and compared to those of an age and sex-matched cohort of 91 patients (Group-2) who had undergone AV access with the traditional venipuncture guided by fluoroscopic landmarks. Results: The two groups were comparable for the success rate of venous access (92.5% versus 93.4%, p = 0.82), complication rate (1.3% versus 0.9%, p = 1.0), and procedure time (71 \pm 32 min versus 70 \pm 29 min, p = 0.9). However, Group-2 had a longer X-ray exposure time (7.6 \pm 8.4 min versus 5.7 \pm 7.3 min, p = 0.03). In Group-1, the univariate logistic regression analysis demonstrated that the AV diameter was associated with successful USGAVA (odds ratio = 3.34, 95% confidence interval 1.47–7.59, p 0.01), with a 3-fold increase of probability of success per each 1 mm increase in the AV diameter. Conclusions: USGAVA using a HUD for CIED implantation is a feasible, effective, and safe technique; moreover, it saves X-ray exposure time without lengthening the implant procedure time.