The purpose of this work was to present body size and tube voltage-dependent equations for optimal selection of image acquisition parameters in guiding clinical X-ray imaging. The dose output of X-ray tubes was expressed as a function of the image acquisition parameters of tube voltage (kVp), tube current–exposure time product (mAs), and body size (d). Dose power (n) to kVp was determined to be a linear function of body size in an earlier phantom study. Tube voltage-dependent attenuation coefficients of water were used to determine the kVp effect on the depth dose of X-rays from the body’s entrance surface. The new expression for the dose output of X-ray tubes in patients was then employed for image quality and radiation dose optimization, assuming that image quality is a logistic function of the radiation dose to patients. For constant kVp, the percentage of mAs increase for a 1-cm increase in body size d is dependent on the kVp applied. For constant mAs, the percentage of kVp increase for a 1-cm increase in body size is dependent on both body size d and the kVp applied. For constant body size, the percentage of kVp increase should be a fraction of the percentage of decrease in the mAs, where the fraction is dependent on the body size. The improved body size and tube voltage-dependent governing equations for variations in X-ray imaging parameters should be more accurate in guiding optimal selection of the kVp and mAs image acquisition parameters in medical X-ray imaging.