Introduction: Quantitative measures of the ventricular fibrillation (VF) ECG waveform predict defibrillation outcomes. A prior study observed that greater Instantaneous Amplitude (IA) of the VF ECG, measured at the instant of defibrillation (Figure), predicted better outcome independent of other VF measures. If true, resuscitation might be improved by synchronizing shock to ECG amplitude. We sought to determine whether IA was an independent predictor of shock-specific outcome using a larger independent dataset. Methods: We investigated adult out-of-hospital VF cardiac arrest cases in a metropolitan EMS system treated with a Philips MRx defibrillator. For each shock, we computed the IA as the absolute value of the ECG at the time of shock delivery. We also computed the amplitude spectrum area (AMSA), a well-characterized waveform measure, from the 3-second CPR-free period preceding the shock. Study outcome was return of spontaneous circulation (ROSC) after each shock. We used Wilcoxon test to evaluate the unadjusted relationship between IA and shock-specific ROSC, and a generalized linear mixed-effect (GLME) model to assess whether IA was associated with shock-specific ROSC independent of AMSA. Results: We included 1516 shocks from 567 patients, with a median (IQR) of 2 (1-3) shocks per patient and shock-specific ROSC rate of 22% (337/1516). IA was correlated with AMSA; Pearson’s R = 0.43. Median (IQR) IA was greater for shocks that resulted in ROSC, with IA of 0.14 (0.05-0.25) mV vs 0.09 (0.04-0.18) mV, (p<0.001). However, when both IA and AMSA were included in a GLME model, AMSA was significantly associated with ROSC (OR 2.09, 95% CI 1.74-2.50 for an IQR change in AMSA) but IA was not (OR 1.04, 95% CI 0.92-1.18 for an IQR change in IA). Conclusions: IA did not independently predict ROSC after controlling for AMSA. Thus, IA is likely a surrogate for other waveform measures, limiting its usefulness to guide instantaneous defibrillation timing as a means to improve outcome.