A sub-dermal structure visualization system and method is disclosed. The system may use an illumination module including: a near-infrared (NIR) light source adapted to substantially uniformly illuminate an imaged area including sub-dermal regions thereof with NIR light; and a first optical system including at least one optical element for controlling at least one of spectral and polarization properties of the NIR light prior to illuminating the imaged area. An imaging module rejects unwanted signals from an imaged area while passing desired optical signals that are to be received by an image acquisition module. The desired optical signals can comprise a vein visualization signal to assist in visualizing a vascular structure below a skin layer of a patient.