Objectives: we compared time-dependent rescue shock success when delivered immediately, to defibrillation preceded by 3 min of CPR, with and without high dose epinephrine (HDE) in a swine model of prolonged ventricular fibrillation (VF). Our hypotheses were that pretreatment with CPR and HDE would produce higher rates of successful first-shock defibrillation and would prevent decay of the VF waveform, as measured by the scaling exponent (ScE), when compared to immediate defibrillation. We also sought to determine the predictive value of the ScE in determining post-shock outcomes. Methods: we anesthetized and instrumented 60 domestic swine (19.6–26.4 kg). VF was induced electrically and was untreated for 8, 11 or 14 min. ECG was recorded digitally at a rate of 1000 samples/s with 5-s epochs used to calculate the ScE. We assigned randomly swine to seven groups (number denotes timing of first rescue shock). Three groups had rescue shocks as the first intervention (RSF) after 8 min of VF (RSF-8), 11 min of VF (RSF-11), or 14 min of VF (RSF-14): two groups had CPR for 3 min (then rescue shock) beginning at 8 min (CPR-11) or 11 min of VF (CPR-14); and two groups got CPR for 3 min with 0.1 mg/kg epinephrine (adrenaline) (then rescue shock) beginning at 8 min of VF (HDE-11) or 11 min of VF (HDE-14). Fixed-dose 70 J BDW rescue shocks were used for all shocks. Defibrillation outcome was classified immediately and 30 s post-shock as successful (either restoration of spontaneous circulation [ROSC] or restoration of organized electrical activity [ROEA]), or failed (remained in VF, or asystole). Data were analyzed with RMANOVA, multiple logistic regression, Fisher's exact tests, and ROC curves. Results: successful first-shock defibrillation occurred in 3/8 (38%) RSF-8; 1/9 (11%) RSF-11; 2/9 (22%) CPR-11; 7/9 (77%) HDE-11; 0/9 (0%) RSF-14; 0/7 (0%) CPR-14; and 1/8 (13%) HDE-14, (p=0.059 IRS-8 vs. HDE-11). First-shock ROSC occurred in 5/9 (56%) HDE-11 animals, 1/8 (13%) HDE-14 and zero in all other groups (p=0.03). Mean ScE values at 11 min VF for the RSF-11 (1.46) was higher than both CPR-11 (1.26), and HDE-11 (1.27); and RSF-14 (1.60) was higher than CPR-14 (1.47) and HDE-14 (1.46); group by time p=0.002. ROC areas under the curves using the ScE as a predictor of shock outcome were 0.84 for immediate success, 0.85 for sustained success, and 0.81 for ROSC. Conclusions: HDE-11 showed a tendency for producing a higher rate of first-shock success and ROSC. Interventions prior to rescue shock prevented deterioration of the VF waveform and improved rescue shock outcomes. The ScE accurately predicted 81–85% of post-rescue shock outcomes.