Introduction: Despite significant advances in resuscitation efforts, there are some patients who remain in ventricular fibrillation (VF) after multiple shocks during out-of-hospital cardiac arrest (OHCA). Double sequential external defibrillation (DSED) has been proposed as a treatment option for patients in shock refractory VF. We sought to compare DSED to standard therapy with regards to VF termination and return of spontaneous circulation (ROSC) for patients presenting in shock refractory VF. Methods: We performed a retrospective review of all treated adult OHCA who presented in VF and received a minimum of three successive shocks over a two year period beginning on Jan 1, 2015 in four Canadian EMS agencies. Using ambulance call reports and defibrillator files, we compared VF termination (defined as the absence of VF at the rhythm check following defibrillation and 2 minutes of CPR) and VF termination into a perfusing rhythm with ROSC between patients who received standard therapy (CPR, defibrillation, epinephrine and antiarrhythmics) and those who received DSED (after on-line medical consultation) for shock refractory VF. Cases of traumatic cardiac arrest and those who presented in VF but terminated VF prior to 3 successive shocks were excluded. Results: Among 197 patients who met the study criteria for shock refractory VF, 161 (81.7%) patients received standard therapy and 36 (18.3%) received DSED. For the primary outcome, VF termination was significantly higher for DSED compared to standard therapy (63.9% vs 18.0%; Δ45.9%; 95% CI: 28.3 to 60.5). For the secondary outcome of VF termination into ROSC, DSED was associated with significantly higher ROSC compared to standard care (33.3% vs 13%; Δ20.3%; 95% CI:13.0 to 33.3). The median (IQR) number of failed standard shocks prior to DSED was 8 (6, 10). When DSED terminated VF, it did so with a single DSED shock in 69.6% of cases. Conclusion: Our observational findings suggest improved VF termination and ROSC are associated with DSED compared to standard therapy for shock refractory VF. An appropriately powered randomized controlled trial is required to assess the impact of DSED on patient-important outcomes.