A mixed preparation consisting of a water-in-oil emulsion-type moisturizing cream and a steroid ointment is frequently prescribed for the treatment of atopic dermatitis. We have investigated the compatibility of moisturizing creams and ointments because there are concerns regarding the physical stability of these mixed preparations. The key technology used in this study was magnetic resonance imaging (MRI). A commercial moisturizing cream and white petrolatum or clobetasone butyrate (CLB) ointment samples were mixed in a weight ratio of 1 : 1. A centrifugation test protocol (20000×g for 3 min) was implemented to accelerate the destabilization processes in the samples. After centrifugation, the mixed preparations separated into three distinct layers (upper, middle, and lower), while no phase separation was observed using moisturizing cream alone. The phase separation was monitored using chemical shift selective images of water and oil and quantitative T2 maps. In addition, MR and near-infrared spectroscopy were employed for component analysis of each phase-separated layer. Collectively, it was confirmed that the lower layer contained water, oils, and organic solvent, while the upper and middle layers were composed solely of oils. Furthermore, this study investigated the distribution of CLB in the phase-separated samples and showed that a heterogeneous distribution existed. From our results, it was confirmed that the mixed preparation became unstable because of the incompatibility of the moisturizing cream and ointment.