Background: The transfemoral (TF) route is the gold-standard access for transcatheter aortic valve replacement (TAVR). In 10-15% of patients, alternative accesses are needed, such as the transcarotid (TC) access. We performed a meta-analysis to compare 30-day mortality and complications between TC-TAVR and TF-TAVR. Methods: We searched PubMed/MEDLINE and EMBASE from inception to January 2021 to identify articles comparing TC-TAVR and TF-TAVR. Patients' baseline characteristics, procedural outcomes, and clinical 30-day outcomes were extracted. Results: We identified 9 studies, among which 2 used propensity-score matching, including 1,374 TC patients and 3,706 TF patients. TC-TAVR was associated with significantly higher EuroSCORE II and Logistic EuroSCORE values (respectively 8.0 ± 6.7 vs. 6.3 ± 5.4, p = 0.002 and 20.8 ± 14.2% vs. 20.0 ± 13.4%, p = 0.04), a higher prevalence of peripheral artery disease (52.6 vs. 32.8%, p = 0.001), previous cardiac surgery (26.3 vs. 22.4%, p = 0.008) and coronary artery disease (64.6 vs. 60.5%, p = 0.020). The pooled results found TC-TAVR to be associated with a significantly higher 30-day mortality risk (RR, 1.41, 95% CI, 1.02-1.96, p = 0.040), and a lower rate of 30-day major vascular complications (RR, 0.48, 95% CI, 0.25-0.92, p = 0.030). No significant difference was found regarding permanent pacemaker implantation, major bleeding and acute kidney injury. A subgroup analysis of the two propensity-score matched studies found a statistically increased risk of 30-day neurovascular complications (RR, 1.61, 95% CI, 1.02-2.55, p = 0.040). Conclusion: Compared with TF-TAVR, TC-TAVR was associated with an increased risk of 30-day mortality, likely related to a higher surgical risk and comorbidity burden, and with an increased risk of 30-day neurovascular complications. Careful preprocedural patient selection and close periprocedural neurological monitoring are paramount.