A simple method to generate well-defined microscopic architectures composed of electrospun nanofibers is reported and their potential application to biomedical fields are described. The photopatterning of polyethylene glycol (PEG) hydrogel on electrospun polycarprolactone (PCL) nanofibers leads to the formation of two different microdomains in nanofibrous mats: a bare nanofiber region and a hydrogel-entrapped nanofiber region. The selective dissolution of bare nanofibers with an organic solvent that cannot penetrate the PEG hydrogel enables the localization of PCL nanofibers within the hydrogel microstructures, thus generating microarchitectured nanofibers. The resultant microarchitectures are easily detached from the substrate by the water-induced swelling of the PEG hydrogel. Microparticles are ultimately obtained, the size and shape of which can be easily controlled with proper photomask designs. In proof of concept experiments, bovine serum albumin(BSA)-loaded PCL nanofibers that are entrapped within the hydrogel microparticles are prepared and the sustained release of BSA from micropatterned nanofibers is successfully demonstrated, indicating the potential application of the proposed microarchitectured nanofibers to drug delivery systems. For another possible application, the capability of the nanofiber-incorporated hydrogel to encapsulate mammalian cells is investigated and the incorporation of nanofibers within the PEG hydrogel promoted cell adhesion and spreading when compared with bare PEG hydrogel is confirmed.