Intraoperative dosimetry in prostate brachytherapy requires localization of the implanted radioactive seeds. A tomosynthesis-based seed reconstruction method is proposed. A three-dimensional volume is reconstructed from Gaussian-blurred projection images and candidate seed locations are computed from the reconstructed volume. A false positive seed removal process, formulated as an optimal coverage problem, iteratively removes "ghost" seeds that are created by tomosynthesis reconstruction. In an effort to minimize pose errors that are common in conventional C-arms, initial pose parameter estimates are iteratively corrected by using the detected candidate seeds as fiducials, which automatically "focuses" the collected images and improves successive reconstructed volumes. Simulation results imply that the implanted seed locations can be estimated with a detection rate of > or = 97.9% and > or = 99.3% from three and four images, respectively, when the C-arm is calibrated and the pose of the C-arm is known. The algorithm was also validated on phantom data sets successfully localizing the implanted seeds from four or five images. In a Phase-1 clinical trial, we were able to localize the implanted seeds from five intraoperative fluoroscopy images with 98.8% (STD=1.6) overall detection rate.