Abstract Background Radial access has become the primary approach for invasive coronary angiography due to its lower complication rate than femoral access. Transcatheter aortic valve implantation (TAVI) frequently requires a secondary access, which has traditionally been femoral access. However, radial access for TAVI is feasible and gaining popularity, but data on its safety and complication rates is still limited. Purpose To evaluate the occurrence of stroke rate in patients undergoing a TAVI procedure with femoral or radial secondary access. Methods A prospective single-center TAVI registry of 2327 patients who received a TAVI procedure between 2019 and 2022 was conducted. All procedures had the primary access over the femoral route. 337 (14.5%) patients had a secondary access over the radial route, whereas 1990 (85.5%) received a femoral secondary access. The primary endpoint was the occurrence of stroke within the hospital stay. Both groups were compared using the t-test or the Mann-Whitney U test according to the distribution of the data. In a second step, a multivariable model was created in which parameters were included that were associated with the endpoint in the previous analysis, as well as parameters that are known to be associated with stroke. Results: Patients were 81.1 ± 6.3 years old, with a Euroscore II of 5.3 ± 6. A total of 610 (26.2%) patients received a balloon-expandable valve. The primary endpoint (stroke within 30 days of the TAVI procedure) was met by 94 (4%) of all patients. Stroke occurred more often in the group with radial secondary access (6.6% (22) vs. 3.6%(72), p = 0.012). Other significant differences between the two groups included (radial vs. femoral access): burden of atrial fibrillation (36.8% vs. 44.6%, p = 0.007), arterial hypertension (87.4% vs. 92%, p = 0.007), Euroscore II (4.6 vs. 5.5, p = 0.006), and frailty (25.2% vs. 40%, p < 0.001). There were no significant differences between the two groups in terms of secondary diagnosis of diabetes or coronary artery disease, age, occurrence of NYHA class III/IV, gender, or cerebral artery disease. In the multivariate analysis including Age, Euroscore II, NYHA class, gender, secondary diagnosis of arterial Hypertension, diabetes or cerebral artery disease, arterial fibrillation, Frailty and radial secondary access, only radial secondary access was independently associated with in-hospital stroke (p = 0.01). Conclusion Radial secondary access was significantly associated with an increased risk of in-hospital stroke following transcatheter aortic valve implantation (TAVI) in our study population. Intense manipulation of the guidewire and catheter to reach the ascending aorta at the beginning of the procedure and to reach the descending aorta for the final angiogram of the primary access vessel may be causative and should be minimized.