Digital tomosynthesis (DTS) based on filtered-backprojection (FBP) reconstruction requires a full field-of-view (FOV) scan and relatively dense projections, which results in high doses for medical imaging purposes. To overcome these difficulties, we investigated region-of-interest (ROI) or interior DTS reconstruction where the x-ray beam span covers only a small ROI containing a target area.An iterative method based on compressed-sensing (CS) scheme was compared with the FBP-based algorithm for ROI-DTS reconstruction. We implemented both algorithms and performed a systematic simulation and experiments on body and skull phantoms. The image characteristics were evaluated and compared.The CS-based algorithm yielded much better reconstruction quality in ROI-DTS compared to the FBP-based algorithm, preserving superior image homogeneity, edge sharpening, and in-plane resolution. The image characteristics of the CS-reconstructed images in ROI-DTS were not significantly different from those in full-FOV DTS. The measured CNR value of the CS-reconstructed ROI-DTS image was about 12.3, about 1.9 times larger than that of the FBP-reconstructed ROI-DTS image.ROI-DTS images of substantially high accuracy were obtained using the CS-based algorithm and at reduced imaging doses and less computational cost, compared to typical full-FOV DTS images. We expect that the proposed method will be useful for the development of new DTS systems.