Background: Cardiac resynchronisation therapy-defibrillator (CRT-D) implantation via the cephalic vein is feasible and safe. Recent evidence has suggested a higher implantable cardioverter defibrillator (ICD) lead failure in multi-lead defibrillator therapy via the cephalic route. We evaluated the relationship between CRT-D implantation via the cephalic and ICD lead failure. Methods: Data was collected from three CRT-D implanting centres between October 2008 – September 2017. In total 631 patients were included. Patient and lead characteristics with ICD lead failure were recorded. Comparison of ‘cephalic’ (ICD lead via cephalic) vs ‘non-cephalic’ (ICD lead via non-cephalic route) cohorts was performed. Kaplan-Meier survival and a Cox-regression analysis were applied to assess variables associated with lead failure. Results: The cephalic and non-cephalic cohorts were equally male (82.2% vs 78.3%, p=0.28), similar in age (69.7±11.5 vs 68.7 ± 11.9, p=0.33) and body mass index (BMI) (27.7±5.1 vs 27.1±5.7, p=0.33). Most ICD leads were implanted via the cephalic vein (73.7%) and patients had a median of 2.8 leads implanted via this route. The rate of ICD lead failure was low and similar between both groups (0.4%/year vs 0.14%/year, p=0.34). Female gender was more common in the lead failure cohort than non-failure (50% vs 18.2%, respectively, p=0.01) as was hypertension (90% vs 54%, respectively, p=0.03). On multivariate Cox regression, female sex (p=0.007), hypertension (p=0.041) and BMI (p=0.042) were significantly associated with ICD lead failure. Conclusion: CRT-D implantation via the cephalic route is not associated with premature ICD lead failure. Female gender, BMI and hypertension correlate with lead failure.