High-performance intraoperative imaging is essential to an ever-expanding scope of therapeutic procedures ranging from tumor surgery to interventional radiology. The need for precise visualization of bony and soft-tissue structures with minimal obstruction to the therapy setup presents challenges and opportunities in the development of novel imaging technologies specifically for image-guided procedures. Over the past -5 years, a mobile C-arm has been modified in collaboration with Siemens Medical Solutions for 3D imaging. Based upon a Siemens PowerMobil, the device includes: a flat-panel detector (Varian PaxScan 4030CB); a motorized orbit; a system for geometric calibration; integration with real-time tracking and navigation (NDI Polaris); and a computer control system for multi-mode fluoroscopy, tomosynthesis, and cone-beam CT. Investigation of 3D imaging performance (noise-equivalent quanta), image quality (human observer studies), and image artifacts (scatter, truncation, and cone-beam artifacts) has driven the development of imaging techniques appropriate to a host of image-guided interventions. Multi-mode functionality presents a valuable spectrum of acquisition techniques: i.) fluoroscopy for real-time 2D guidance; ii.) limited-angle tomosynthesis for fast 3D imaging (e.g., -10 sec acquisition of coronal slices containing the surgical target); and iii.) fully 3D cone-beam CT (e.g., -30-60 sec acquisition providing bony and soft-tissue visualization across the field of view). Phantom and cadaver studies clearly indicate the potential for improved surgical performance - up to a factor of 2 increase in challenging surgical target excisions. The C-arm system is currently being deployed in patient protocols ranging from brachytherapy to chest, breast, spine, and head and neck surgery.