Background— The Navvus pressure sensor–equipped microcatheter allows to measure functional stenosis severity over a work-horse guidewire and is used as a more feasible alternative to regular sensor-equipped wires. However, Navvus is larger in diameter than contemporary sensor-equipped guidewires and may, thereby, influence functional measurements. The present study evaluates the hemodynamic influence of the Navvus microcatheter. Methods and Results— In patients with intermediate coronary stenosis, coronary pressure and flow velocity were measured using a dual sensor–equipped guidewire before and after introduction of Navvus. Patients were randomized to microcatheter-first or guidewire-first measurement. The primary end point was the difference in hyperemic stenosis resistance index between measurements before and after introduction of Navvus. Measurements were completed in 28 patients (28 stenoses). Mean hyperemic stenosis resistance was 0.37±0.19 Hg/cm/s for wire-only assessment and 0.48±0.26 Hg/cm/s after Navvus introduction ( P <0.001). Bland–Altman analysis documented a mean bias of +0.11 Hg/cm/s (limits of agreement: −0.13 to 0.36), proportional to mean hyperemic stenosis resistance (Spearman ρ =0.61; P =0.001). Passing–Bablok analysis revealed absence of a constant difference but significant proportional difference between the methods. Mean fractional flow reserve was 0.86±0.06 for wire-only assessment and 0.82±0.07 after Navvus introduction ( P <0.001). Bland–Altman analysis documented a mean bias of −0.033 (limits of agreement: −0.09 to 0.03), proportional to mean fractional flow reserve (Spearman ρ =0.40; P =0.036). Passing–Bablok analysis revealed significant constant and proportional differences between methods. Similar results were documented for resting indices of stenosis severity. Conclusions— Introduction of the Navvus microcatheter leads to clinically relevant stenosis severity overestimation in intermediate stenosis.