Embodiments herein relate to systems and methods for rapidly calibrating optical medical sensors. In an embodiment, a method can include placing a reflective optical medical sensor device on or in a patient. The reflective optical medical sensor device can include one or more optical emitters; one or more optical detectors; and a measurement circuit having one or more transimpedance amplifiers (TIA). The method can include setting the TIA to a fixed gain value and then turning on the optical emitter associated with each spatially unique measurement vector and receiving reflected light with the associated optical detector for each spatially unique measurement vector at the same fixed gain value. The method can include assessing the signal-to-noise (SNR) for each spatially unique measurement vector and selecting the spatially unique measurement vector having the highest SNR. Other embodiments are also included herein.