OBJECTIVE: Arterial transfer functions (TFs) describe the relationship between the pressure waveform at different arterial sites. Generalized TFs are used to reconstruct central aortic waveforms from non-invasively obtained peripheral waveforms and have been promoted as potentially clinically useful. A limitation is the paucity of information on their 'generalizability' with no information existing on the number of subjects required to construct a satisfactory TF, nor is adequate prospective validation available. We therefore investigated the uniformity of radial-aortic TFs and prospectively estimated the capacity of a generalized TF to reconstruct individual central blood pressure parameters. PATIENTS AND METHODS: Ninety-three subjects (64 male) were studied by simultaneous radial applanation and high-fidelity (Millar Mikro-tip catheter) direct measurement of central aortic BP during elective coronary procedures. Subjects were prospectively randomized to either a derivation or validation group. RESULTS: Increasing numbers of individual TFs from the derivation group were averaged to form a generalized TF. There was minimal change with greater than 20 TFs averaged. In the validation group, the error in most reconstructed parameters related to the absolute value of the directly measured parameter [systolic blood pressure (SBP) and pulse pressure, P<0.05; systolic pressure-time interval, subendocardial viability index, augmentation index, and times to the inflection point, peak and end systole, all P<0.01]. Aorto-radial delay was related to error in reconstructed central aortic SBP and pulse pressure (negatively) and time to peak systole (positively) (all P<0.001). Reconstruction of augmentation index was poor. DISCUSSION: Inclusion of more than 20 individual TFs in the construction of a generalized TF does not improve 'generalizability'. There appear to be systematic errors in derived central pressure waveforms and derived aortic augmentation index is inaccurate compared to the directly measured value.