AIMS: Approximately 5.7% of potential subcutaneous implantable cardioverter-defibrillator (S-ICD) recipients are ineligible by virtue of their vector morphology, with higher rates of ineligibility observed in some at-risk groups. Mathematical vector rotation is a novel technique that can generate a personalized sensing vector, one with maximal R:T ratio, using electrocardiogram (ECG) signal recorded from the present S-ICD location. METHODS AND RESULTS: A cohort of S-ICD ineligible patients were identified through ECG screening of ICD patients with no ventricular pacing requirement and their personalized vectors were generated using ECG signal from a Holter monitor. Subcutaneous ICD eligibility in this cohort was then recalculated. In a separate cohort, episodes of arrhythmia were recorded in patients undergoing arrhythmia induction, and arrhythmia detection in standard S-ICD vectors was compared to rotated vectors using an S-ICD simulator. Ninety-two participants (mean age 64.9 ± 2.7 years) underwent screening and 5.4% were found to be S-ICD ineligible. Personalized vector generation increased the R:T ratio in these vectors from 2.21 to 7.21 (4.54-9.88, P < 0.001) increasing the cohort eligibility from 94.6% to 100%. Rotated S-ICD vectors also showed high ventricular fibrillation (VF) detection sensitivity (97.8%), low time to VF detection (6.1 s), and excellent tachycardia discrimination (sensitivity 96%, specificity 88%), with no significant differences between rotated and standard vectors. CONCLUSION: In S-ICD ineligible patients, mathematical vector rotation can generate a personalized vector that is associated with a significant increase in R:T ratio, resulting in universal device eligibility in our cohort. Ventricular fibrillation detection efficacy, time to VF detection, and tachycardia discrimination were not affected by vector rotation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.