Introduction: Electrophysiology (EP) procedures are nowadays the gold-standard method for tachyarrhythmia treatment with impressive success rates, but also with a considerable risk of complications, mainly vascular. A systematic review and meta-analysis was performed to evaluate the safety of ultrasound (US)-guided femoral vein access in EP procedures compared to the traditional anatomic landmark-guided method. Methods: We searched Pubmed (MEDLINE), Embase, Web of Science, and Cochrane electronic databases for relevant entries, dated from January 1st, 2000 to June 30th, 2021. Only observational studies and randomized controlled trials were included in this analysis. Data extraction included study details, patient characteristics, procedure details, and all types of vascular complications. Complications were classified as major if any intervention, prolongation of hospitalization, or readmission was required. Results: 9 studies (1 randomized controlled trial and 8 observational), with 7,858 participants (3,743 in the US-guided group, 4,115 in the control group), were included in the meta-analysis. Overall vascular complication rates were significantly decreased in the US-guided group compared to the control group (1.2 versus 3.2%, RR = 0.38, 95% CI, 0.27 - 0.53), in all EP procedures. Sub-group analysis of AF ablation procedures yielded similar results (RR 0.41, 95% CI, 0.29 - 0.58, p < 0.00001). The event reduction effect was significant for both major and minor vascular complications. Conclusion: US-guided vascular access in EP procedures is associated with significantly reduced vascular complications, compared to the standard anatomic landmark-guided approach, regardless of procedure complexity.