The physicochemical properties and drug release characteristics of Q1/Q2 equivalent microspheres are sensitive to minor manufacturing changes, which may alter their stability under different storage-conditions. This may be undesirable due to the presence of a substantial amount of drug in microsphere products. Hence, the objective of the present work was to investigate the impact of minor manufacturing changes on the stability of Q1/Q2 equivalent microspheres under various storage conditions. Two Q1/Q2 equivalent risperidone microsphere formulations prepared with minor manufacturing changes (solvent system etc.) showed differences in their physicochemical properties (size, morphology, porosity etc.), drug release characteristics and hence, storage stability. Overall, both formulations were stable under long-term storage conditions (4 °C/ambient humidity). However, under the intermediate storage conditions (25 °C/ambient humidity), only formulation 1 was stable while formulation 2 showed significant polymer degradation, particle aggregation and alteration in the drug release characteristics. Lastly, under accelerated storage conditions (40 °C/ambient humidity vs 75% RH), the extent of polymer degradation, morphological changes and alteration of drug release characteristics of formulation 2 was significantly higher compared to that of formulation 1. Thus, minor manufacturing changes have the potential to significantly alter the storage stability and, hence, the quality and performance of complex drug products such as microspheres.