Continuous measurement of cerebral blood flow velocity (CBFV) of the middle cerebral artery (MCA) using transcranial Doppler (TCD) and arterial blood pressure (ABP) monitoring enables assessment of cerebrovascular haemodynamics. Further indices describing cerebrovascular function can be calculated from ABP and CBFV, such as the mean index (Mxa) of cerebrovascular autoregulation, the 'time constant of the cerebral arterial bed' (tau), the 'critical closing pressure' (CrCP) and a 'non-invasive estimator of ICP' (nICP). However, TCD is operator-dependent and changes in angle and depth of MCA insonation result in different readings of CBFV. The effect of differing CBFV readings on the calculated secondary indices remains unknown. The aim of this study was to investigate variation in angle and depth of MCA insonation on these secondary indices. In eight patients continuous ABP and ipsilateral CBFV monitoring was performed using two different TCD probes, resulting in four simultaneous CBFV readings at different angles and depths per patient. From all individual recordings, the K-means clustering algorithm was applied to the four simultaneous longitudinal measurements. The average ratios of the between-clusters, sum-of-squares and total sum-of-squares were significantly higher for CBFV than for the indices Mxa, tau and CrCP (p < 0.001, p = 0.007 and p = 0.016) but not for nICP (p = 0.175). The results indicate that Mxa, tau and CrCP seemed to be not affected by depth and angle of TCD insonation, whereas nICP was.