The three-volume set LNCS 8149, 8150, and 8151 constitutes the refereed proceedings of the 16th International Conference on Medical Image Computing and Computer-Assisted Intervention, MICCAI 2013, held in Nagoya, Japan, in September 2013. Based on rigorous peer reviews, the program committee carefully selected 262 revised papers from 789 submissions for presentation in three volumes. The 95 papers included in the first volume have been organized in the following topical sections: physiological modeling and computer-assisted intervention; imaging, reconstruction, and enhancement; registration; machine learning, statistical modeling, and atlases; computer-aided diagnosis and imaging biomarkers; intraoperative guidance and robotics; microscope, optical imaging, and histology; cardiology, vasculatures and tubular structures; brain imaging and basic techniques; diffusion MRI; and brain segmentation and atlases.