The orifice drilled in the membrane as a channel for drug delivery is the key functional part of the osmotic pumps for a controlled drug release system. Reported conventional microscopic evaluations of these orifices have been limited to measurement of two-dimensional cross-section diameters. This study was aimed at establishing a novel method to measure quantitatively the three-dimensional architectures of orifices based on synchrotron radiation X-ray microcomputed tomography (SR-μCT). Quantitative analysis of architectures extracted from captopril osmotic pumps drilled by a range of operating parameters indicated that laser power correlated with the cross section area, volume, surface area and depth of the orifices, while scanning speed of laser beam showed inverse relationships with the above structure characters. The synchrotron radiation based Fourier transform infrared microspectroscopy mapping showed that there was no apparent chemical change in the surrounding area of the orifice compared with the normal membrane region. Thus SR-μCT was successfully applied to marketed felodipine osmotic pumps for architectural evaluation of the orifices. In conclusion, the first three-dimensional structural insight of orifices in osmotic pump tablets by SR-μCT and structural reconstruction for the architectures has provided deeper insight into improving the design of advanced osmotic pumps for controlled drug release.