Abstract OBJECTIVES The transcarotid (TC) approach for transcatheter aortic valve implantation (TAVI) is potentially an optimal alternative to the transfemoral (TF) approach. Our goal was to compare the safety and efficacy of TC- and TF-TAVI. METHODS Patients who underwent TF-TAVI or TC-TAVI in the prospectively collected FRANCE TAVI registry between January 2013 and December 2015 were compared. Propensity score inverse probability weighting methods were employed to minimize the impact of bias related to non-random treatment assignment. RESULTS Of the 11 033 patients included in the current study, 10 598 (96%) underwent a TF-TAVI and 435 (4.1%) had a TC-TAVI. Patients in the TC-TAVI access group presented with a higher risk profile but were significantly younger. There were no differences in the perioperative and 2-year mortality rates after adjustment [odds ratio (OR) 1.02, 95% confidence interval (CI) 0.62–1.68; P = 0.99 and hazard ratio 1.03, 95% CI 0.7–1.35; P = 0.83). TC-TAVI was associated with a significant risk of stroke (OR 2.42, 95% CI 2.01–2.92; P < 0.001), ST-elevation myocardial infarction (OR 7.32, 95% CI 3.87–13.87; P < 0.001), infections (OR 2.36, 95% CI 2.04–2.71; P < 0.001), bleeding (OR 2.01, 95% CI 1.76–2.29; P < 0.001), renal failure (OR 2.23, 95% CI 1.90–2.60; P < 0.001) and need for dialysis (OR 2.36, 95% CI 2.01–2.76, P < 0.001). Conversely, TC-TAVI was not confirmed as a risk factor for pacemaker implantation after adjustment (OR 1.05, 95% CI 0.96–1.15; P < 0.28) and was a protective factor for vascular complications (OR 0.37, 95% CI 0.32–0.43; P < 0.001). CONCLUSIONS TC-TAVI is a safe procedure compared to TF-TAVI, although it holds an increased risk of perioperative complications. It should be considered in case of non-femoral peripheral access as the second access choice, to increase the overall safety of TAVI procedures.