Endovascular aortic repair is an emerging novel intervention for the management of abdominal aortic aneurysms. It is crucial to compare the effectiveness of different access sites, such as transfemoral access (TFA) and upper extremity access (UEA). An electronic literature search was conducted using PubMed, EMBASE, and Google Scholar databases. The primary endpoint was the incidence of stroke/transient ischemic attack (TIA), while the secondary endpoints included technical success, access-site complications, mortality, myocardial infarction (MI), spinal cord ischemia, among others. Forest plots were constructed for the pooled analysis of data using the random-effects model in Review Manager, version 5.4. Statistical significance was set at p < 0.05. Our findings in 9403 study participants (6228 in the TFA group and 3175 in the UEA group) indicate that TFA is associated with a lower risk of stroke/TIA [RR: 0.55; 95% CI: 0.40–0.75; p = 0.0002], MI [RR: 0.51; 95% CI: 0.38–0.69; p < 0.0001], spinal cord ischemia [RR: 0.41; 95% CI: 0.32–0.53, p < 0.00001], and shortens fluoroscopy time [SMD: −0.62; 95% CI: −1.00 to −0.24; p = 0.001]. Moreover, TFA required less contrast agent [SMD: −0.33; 95% CI: −0.61 to −0.06; p = 0.02], contributing to its appeal. However, no significant differences emerged in technical success [p = 0.23], 30-day mortality [p = 0.48], ICU stay duration [p = 0.09], or overall hospital stay length [p = 0.22]. Patients with TFA had a lower risk of stroke, MI, and spinal cord ischemia, shorter fluoroscopy time, and lower use of contrast agents. Future large-scale randomized controlled trials are warranted to confirm and strengthen these findings.