We present a method to automatically segment 4D flow magnetic resonance imaging (MRI) by identifying net flow effects using the standardized difference of means (SDM) velocity. The SDM velocity quantifies the ratio between the net flow and observed flow pulsatility in each voxel. Vessel segmentation is performed using an F-test, identifying voxels with significantly higher SDM velocity values than background voxels. We compare the SDM segmentation algorithm against pseudo-complex difference (PCD) intensity segmentation of 4D flow measurements in in vitro cerebral aneurysm models and 10 in vitro Circle of Willis (CoW) datasets. We also compared the SDM algorithm to convolutional neural network (CNN) segmentation in 5 thoracic vasculature datasets. The in vitro flow phantom geometry is known, while the ground truth geometries for the CoW and thoracic aortas are derived from high-resolution time-of-flight (TOF) magnetic resonance angiography and manual segmentation, respectively. The SDM algorithm demonstrates greater robustness than PCD and CNN approaches and can be applied to 4D flow data from other vascular territories. The SDM to PCD comparison demonstrated an approximate 48% increase in sensitivity in vitro and 70% increase in the CoW, respectively; the SDM and CNN sensitivities were similar. The vessel surface derived from the SDM method was 46% closer to the in vitro surfaces and 72% closer to the in vitro TOF surfaces than the PCD approach. The SDM and CNN approaches both accurately identify vessel surfaces. The SDM algorithm is a repeatable segmentation method, enabling reliable computation of hemodynamic metrics associated with cardiovascular disease.