Noninvasive fractional flow reserve (FFR) from coronary computed tomography angiography (cCTA) correlates well with invasive FFR and substantially improves the detection of obstructive coronary artery disease. However, with current algorithms, computed tomography (CT)-based FFR is derived off-site in an involved time-consuming manner. We sought to investigate the diagnostic performance of a novel CT-based FFR algorithm, developed for time-efficient in-hospital evaluation of hemodynamically indeterminate coronary lesions. In a blinded fashion, CT-based FFR was assessed in 67 coronary lesions of 53 patients. Pressure guidewire-based FFR <0.80 served as the reference standard to define hemodynamically significant stenosis and assess the diagnostic performance of CT-based FFR compared with standard evaluation of cCTA (luminal diameter stenosis of ≥50%). We recorded the time needed for derivation of CT-based FFR. On a per-lesion and per-patient basis, CT-based FFR resulted in a sensitivity of 85% and 94%, a specificity of 85% and 84%, a positive predictive value of 71% and 71%, and a negative predictive value of 93% and 97%, respectively. The area under the receiver operating characteristic curve on a per-lesion basis was significantly greater for CT-based FFR compared with standard evaluation of cCTA (0.92 vs 0.72, p = 0.0049). A similar trend, albeit not statistically significant, was observed on per-patient analysis (0.91 vs 0.78, p = 0.078). Mean total time for CT-based FFR was 37.5 ± 13.8 minutes. In conclusion, the CT-based FFR algorithm evaluated here outperforms standard evaluation of cCTA for the detection of hemodynamically significant stenoses while allowing on-site application within clinically viable time frames.