BACKGROUND & AIMS: Pharyngeal manometry and impedance provide information on swallow function. We developed a new analysis approach for assessment of aspiration risk. METHODS: We studied 20 patients (30-95 years old) with suspected aspiration who were referred for videofluoroscopy, along with controls (ages 24-47 years). The pharyngeal phase of liquid bolus swallowing was recorded with manometry and impedance. Data from the first swallow of a bolus and subsequent clearing swallows were analyzed. We scored fluoroscopic evidence of aspiration and investigated a range of computationally derived functional variables. Of these, 4 stood out as having high diagnostic value: peak pressure (PeakP), pressure at nadir impedance (PNadImp), time from nadir impedance to peak pressure (TNadImp-PeakP), and the interval of impedance drop in the distal pharynx (flow interval). RESULTS: During 54 liquid, first swallows and 40 clearing swallows, aspiration was observed in 35 (13 patients). Compared to those of controls, patient swallows were characterized by a lower PeakP, higher PNadImp, longer flow interval, and shorter TNadImp-PeakP. A Swallow Risk Index (SRI), designed to identify dysfunctions associated with aspiration, was developed from iterative evaluations of variables. The average first swallow SRI correlated with the average aspiration score (r = 0.846, P < .00001 for Spearman Rank Correlation). An average SRI of 15, when used as a cutoff, predicted aspiration during fluoroscopy for this cohort (kappa = 1.0). CONCLUSIONS: Pressure-flow variables derived from automated analysis of combined manometric/impedance measurements provide valuable diagnostic information. When combined into an SRI, these measurements are a robust predictor of aspiration.