Background <p>Multiple protocols for acquiring intracranial four-dimensional flow magnetic resonance (4D Flow MR) data and post-processing software employed to obtain hemodynamic parameters are available. However, insufficient validation exists to quantify the difference in measurements. This study aims to perform a comprehensive cross-comparison analysis of quantitative results from three major vendors and three post-processing software platforms.</p> Methods <p>Intracranial 4D Flow MR was conducted on 20 healthy volunteers using three different 3.0T MRI scanners. For each subject, nine major intracranial arteries (a total of 180 arteries) were analyzed using three post-processing software platforms: CVI42, MASS, and TS FLOW. Key hemodynamic parameters—including flow rate, maximum velocity (Vmax), average velocity (Vavg), and delineated vessel area—was extracted. The study compared results across different vendors and software, and further assessed both intra-observer and inter-observer consistency.</p> Results <p>Regardless of the post-processing software used, no significant differences were observed in the flow rate across different scanners (<i>p</i> &gt; 0.05), with ICC = 0.700-0.919 and equivalence testing results indicate the interchangeable use of all three scanners. For flow rate and Vmax, the MASS and CVI42 software were equivalent. For Vavg, TS FLOW and CVI42 were tested equivalent. For vessel area, various agreement was shown across software (ICC = 0.083–0.577). Additionally, the TS FLOW software exhibited repeatability and reproducibility (intra-observer ICC = 0.724–0.998; inter-observer ICC = 0.590–0.981).</p> Conclusions <p>Scanning protocols by different vendors appear to result in smaller variations in flow rate compared to using different post-processing software methods. It is recommended to employ single post-processing software or conduct software calibration when using multiple software platforms to ensure consistency in multi-center clinical studies.</p>