Abstract Background Non-pulmonary vein (PV) triggers play a role in the initiation of atrial fibrillation (AF), with the superior vena cava (SVC) being a common location. The aim of the current study was to investigate a strategy of empirical SVC isolation (SVCI) in addition to re-isolation of PV in patients with recurrence of AF after index PV isolation (PVI). Methods We retrospectively analyzed consecutive patients from two centers with recurrence of AF after index PVI, undergoing a repeat ablation. Whereas only a re-isolation of the PV was intended in patients with reconnections of equal or more than two PV (PVI group), an additional SVCI was aimed for in patients with < 2 isolated PV in addition to the re-isolation of the PV (PVI + group). Analysis was performed as-treated and per-protocol. Results Of the 344 patients included in the study (age 60 ± 10 years, 73% male, 66% paroxysmal AF), PVI only was performed in 269 patients (77%) and PVI plus SVCI (PVI +) in 75 patients (23%). Overall, freedom from AF/AT after repeat PVI was 80% (196 patients) in the PVI group and 73% in the PVI + group (p = 0.151). In multivariable Cox regression analysis, presence of persistent AF (HR 2.067 (95% CI 1.389–3.078), p < 0.001) and hypertension (HR 1.905 (95% CI 1.218–2.980), p = 0.005) were identified as only significant predictors of AF/AT recurrence. The per-protocol results did not differ from this observation. Conclusions A strategy of an empirical additional SVCI at repeat PVI ablation for recurrence of AF/AT does not improve outcome compared to a PVI only approach.