Carotid femoral pulse wave velocity (cfPWV) is the 'gold standard' for assessment of arterial stiffness. The reliability of cfPWV measurement depends on the estimation of pulse transit time (PTT). This study aimed to validate a region-matching method for determining PTT and cfPWV against the existing 'foot-to-foot' methods. A cohort of 81 subjects (33 males and 48 females) aged 25-80 (45.1±15.7 years) were studied. PTTs were estimated by the region matching and 'foot-to-foot' methods ('diastole minimum', 'maximum first derivative', 'maximum second derivative' and 'tangent intersection' methods) with manual identification as the reference method and were subsequently used to calculate cfPWV. In a subgroup of 30 individuals, the measurements were repeated after 1 h. There were excellent correlations between cfPWV obtained by the reference method and all the estimated methods (r>0.9, P<0.001 for all), except the diastole minimum method (r=0.793, P<0.001). The region-matching method yielded cfPWV with a better accuracy (mean difference=-0.161 m s(-1), limits of agreement: -0.79 to 0.46 m s(-1)) and repeatability (mean difference=-0.228 m s(-1), intraclass correlation coefficient=0.957) comparing with the 'foot-to-foot' methods. These results demonstrate that the proposed region-matching method is more accurate and suitable for PTT estimation and cfPWV measurement.