In this article, the nucleation process of cefodizime sodium was analyzed from two perspectives: induction time and hydrogen-bond formation. According to classical nucleation theory, the correlation of the induction time indicated that heterogeneous nucleation dominates the nucleation process at lower supersaturation whereas homogeneous nucleation is the main mechanism at higher supersaturation. Then, in situ Raman spectroscopy was used to investigate the probability of hydrogen-bond formation in the supersaturated solution and the nucleation process of cefodizime sodium. A central feature of the hydrogen bonding is that the probability reaches a maximum value at the nucleation point, which can be used to relate the probability of hydrogen-bond formation to the induction time. Furthermore, SEM imaging affords fundamental information to illustrate the effect of supersaturation on the morphology of cefodizime sodium crystals: agglomerated small needlelike particles preferentially formed at a high supersaturation, whereas large needlelike particles formed at low supersaturation.