Objective A better understanding of the effect of position on intracranial pressure (ICP) and compliance is important for the development of treatment strategies that can restore the normal cerebrospinal fluid (CSF) dynamics. There is limited knowledge of the effect of position on intracranial compliance. In this cross-sectional study we tested the association of pulse amplitude with position and day/night cycle. Additionally, we describe the postural ICP and pulse amplitude changes of patients with ‘normal’ ICP dynamics. Methods This single-centre retrospective study included patients with suspected/confirmed CSF dynamics abnormalities who were investigated with elective 24-hour ICP monitoring between October 2017 and September 2019. Patients were enrolled in a short exercise battery including 4 positions: supine, lumbar puncture position in left lateral decubitus, sitting and standing. Each position was maintained for 2 minutes, mean ICP and pulse amplitude were calculated for each position. 24-hour, day and night median ICP and pulse amplitude data were also collected. Linear regression models were used to test the correlation of pulse amplitude with position and day/night cycle. All linear regressions were corrected for confounders. The postural ICP monitoring results of patients without obvious ICP dynamic abnormality were summarised. Results 101 patients (24 males and 77 females) with a mean age of 39 years (±13SD), were included in the study. The adjusted linear regression models demonstrated a significant association of ICP with position and day/night cycle, resulting in upright (sitting and standing) and day ICP being lower than supine/night ICP values. The adjusted linear regression model was also significant for the association of pulse amplitude with position and day/night cycle, resulting in upright and day pulse amplitude being higher than supine/night pulse amplitude results. These associations were confirmed for patients with and without shunts. Patients without clear ICP dynamics abnormality had a tighter control of the postural ICP changes compared to the other patients, however, the difference between groups was not statistically significant. Conclusions This is the largest study investigating the effect of postural changes on intracranial compliance. The results of this study suggest that pulse amplitude (as well as ICP) is significantly associated with posture, increasing in upright positions compared to supine. Further studies will be needed to investigate the mechanism behind this association.