A simplified formula to calculate the predicted fractional flow reserve (FFR) in sequen-tial coronary stenosis without balloon inflation is hereby proposed. In patients with an indication for FFR and sequential coronary stenosis, FFR was recorded distally and between the lesions. The predicted FFR for each stenosis was calculated with a novel formu-la. While treating one of the lesions, wedge pressure was measured during balloon inflation to calculate Pijls' formula. FFR of the remaining lesion was finally recorded (measured FFR). Forty patients were enrolled in the study, 4 (10.0%) had a distal FFR > 0.80 and were excluded from the main analysis. In the remaining 36 patients, the novel formula and Pijls' formula showed virtually absolute agreement (ICCa 0.999, R2 = 0.997 for the proximal lesion, R2 = 0.999 for the distal lesion, kappa 1.000, Se 100%, Sp 100%). The agreement between predicted and measured FFR was good (ICCa 0.820; 0.640-0.909, R2 = 0.717, intercept = 0.05, slope = 0.92, kappa 0.748, Se 75%, Sp 96%). In 19 (47.5%) cases the use of the formula enabled the operator to freely decide which lesion should be treated first, an option not available if the percutaneous coronary intervention (PCI) were guided by the largest pressure drop across each lesion. The predicted FFR for each lesion in sequential coronary stenosis can be accurately calculated by a simplified formula circumventing the need for balloon inflation. This approach provides the operator upfront, with detailed information on physiology, thus having a potentially high impact on the corresponding PCI strategy.