Background: Transcatheter aortic valve implantation is indicated in high-risk patients with aortic stenosis. We compared the clinical outcome of 180 consecutive patients who underwent transapical (TA) and transfemoral (TF) procedures in a single centre. Methods: Ninety consecutive TA (TA-group) and 90 consecutive TF (TF-group) were performed from 2009 to 2014. Clinical variables were prospectively collected and retrospectively analysed for hospital outcomes and to identify risk factors for hospital mortality, vascular complications and stroke. Results: Mean age was 80 +/- 8.5 and 83 +/- 8.4 years, in the TA and TF-group, respectively. TA-group presented higher prevalence of comorbidities: more vascular disease (79% vs 22%, p < 0.001), chronic pulmonary disease (32% vs 10%, p < 0.001), previous vascular surgery (14% vs 4%, p = 0.039), coronary disease (60% vs 40%, p = 0.007), and previous cardiac surgery (28% vs 17%, p = 0.073). Logistic Euroscore was 36 +/- 15% in the TA-group and 25 +/- 14% in the TF-group (p < 0.001), but hospital mortality was similar (TA:9%, TF:10%, p = 0.799). Access-related vascular complications occurred more often in transfemoral patients (TA:3%, TF: 11%, p = 0.081) while major bleeding (TA:3%, TF:4%, p = 1) and stroke (TA: 2%, TF:3%, p = 1) were equally distributed. Postoperative renal failure and dialysis were associated with impaired neurological outcome (p = 0.035 and p = 0.020, respectively). Mild to severe paravalvular leak was more prevalent in transfemoral patients (TA:5%, TF:25%, p < 0.001). Conclusions: In our experience, the TA and TF-group presented different risk profiles but mortality rate and adverse neurological outcome had a similar incidence. The transfemoral approach carried more vascular complications and paravalvular leaks but last-generation devices will improve this outcome.