We report methodological advances that enhance the phosphorescence efficiency of a blue-emitting calcium aluminate phosphor (CaAl2O4: Eu2+, Nd3+). The investigation of long-persistence blue-emitting phosphors is highly desirable due to their promising applications, such as white LEDs; however, the development of highly efficient blue-emitting phosphors is still challenging. Here, we have quantitatively characterized the phosphorescence properties of the blue-emitting phosphor CaAl2O4:Eu2+, Nd3+ with various compositions and directly related these properties to the quality of its luminescence. We optimized the composition of the activator Eu2+ and the co-activator Nd3+, the doping conditions with alkaline earth metals, alkali metals, and Si to create crystallographic distortions and, finally, the flux conditions to find the best parameters for bright and persistent blue-emitting phosphors. Our research has identified several doping compositions with good to excellent performance, with which we have demonstrated bright and persistent phosphors with afterglow characteristics superior to those of conventional phosphors.