<p>Plaque accumulation in coronary arteries causes stenoses, reducing blood flow and increasing the risk of cardiovascular disorders such as heart attacks. To assess the physiological impact of blood pressure across a stenosis, commercial pressure guidewires measure the fractional flow reserve using optical, piezoresistive or piezoelectric sensors, which suffer from brittleness, limited manoeuvrability and high costs. Here we report an iontronic tip-sensing guidewire (ITG) that integrates a thin iontronic tip sensor in a commercial workhorse guidewire via iontronic-based signal transmission, leveraging the ionic nature of human tissues. Intravascular pressure changes induce a capacitance difference at the interface of the metal and ionic gel of the ITG, allowing detection of subtle pressure changes in blood flow, substantially outperforming commercial guidewires. The ITG is free of embedded conductive leads needed in other pressure guidewires to ensure an ideal torque ratio for high manoeuvrability, and we validated its effectiveness and sensitivity in rabbit, goat and pig models in vivo. The compatibility of the ITG with commercial horsework guidewires will upgrade the design of interventional medical devices.</p>