Oropharyngeal swallowing involves complex neuromodulation to accommodate changing bolus characteristics. The pressure events during deglutitive pharyngeal reconfiguration and bolus flow can be assessed quantitatively using high-resolution pharyngeal manometry with impedance. An 8-French solid-state unidirectional catheter (32 pressure sensors, 16 impedance segments) was used to acquire triplicate swallows of 3 to 20 ml across three viscosity levels using a Standardized Bolus Medium (SBMkit) product (Trisco, Pty. Ltd., Australia). An online platform (https://swallowgateway.com/; Flinders University, South Australia) was used to semiautomate swallow analysis. Fifty healthy adults (29 females, 21 males; mean age 46 yr; age range 19-78 yr old) were studied. Hypopharyngeal intrabolus pressure, upper esophageal sphincter (UES) maximum admittance, UES relaxation pressure, and UES relaxation time revealed the most significant modulation effects to bolus volume and viscosity. Pharyngeal contractility and UES postswallow pressures elevated as bolus volumes increased. Bolus viscosity augmented UES preopening pressure only. We describe the swallow modulatory effects with quantitative methods in line with a core outcome set of metrics and a unified analysis system for broad reference that contributes to diagnostic frameworks for oropharyngeal dysphagia.NEW & NOTEWORTHY The neuromodulation of the healthy oropharyngeal swallow response was described in relation to bolus volume and viscosity challenges, using intraluminal pressure and impedance topography methods. Among a wide range of physiological measures, those indicative of distension pressure, luminal opening, and flow timing were most significantly altered by bolus condition, and therefore can be considered to be potential markers of swallow neuromodulation. The study methods and associated findings inform a diagnostic framework for swallow assessment in patients with oropharyngeal dysphagia.