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In this paper, we present a novel image enhancement approach using a color shift model-based multiple color-filter aperture (MCA) camera for digital multifocusing. The proposed image enhancement algorithm consists of three steps; (i) cluster-based region-of-interest (ROI) estimation, (ii) image registration using phase correlation matching (PCM) and fusion, and (iii) image enhancement using spatially adaptive noise smoothing based on the alpha map. The image acquired by the MCA configuration contains color misalignment, which provides additional depth information of objects at different distances. This color misalignment can also provide additional information for blur estimation. The proposed cluster-based image segmentation method can effectively classify ROIs according to the distance from the camera. The segmented regions are aligned by using PCM, and they are fused to generate an in-focused image. For further enhancement of the color-registered image, we use spatially adaptive noise smoothing based on the alpha map. Experimental results show the proposed image enhancement method can significantly enhance the visual quality of the MCA output image, and can be fully or partially incorporated into multifocusing or extended depth of field (EDoF) systems in the form of the finite impulse response (FIR) filter structure.