Intraoperative imaging could improve patient safety and quality assurance (QA) via the detection of subtle complications that might otherwise only be found hours after surgery. Such capability could therefore reduce morbidity and the need for additional intervention. Among the severe adverse events that could be more quickly detected by high-quality intraoperative imaging is acute intracranial hemorrhage (ICH), conventionally assessed using post-operative CT. A mobile C-arm capable of high-quality cone-beam CT (CBCT) in combination with advanced image reconstruction techniques is reported as a means of detecting ICH in the operating room. The system employs an isocentric C-arm with a flat-panel detector in dual gain mode, correction of x-ray scatter and beam-hardening, and a penalized likelihood (PL) iterative reconstruction method. Performance in ICH detection was investigated using a quantitative phantom focusing on (non-contrast-enhanced) blood-brain contrast, an anthropomorphic head phantom, and a porcine model with injection of fresh blood bolus. The visibility of ICH was characterized in terms of contrast-to-noise ratio (CNR) and qualitative evaluation of images by a neurosurgeon. Across a range of size and contrast of the ICH as well as radiation dose from the CBCT scan, the CNR was found to increase from ∼2.2-3.7 for conventional filtered backprojection (FBP) to ∼3.9-5.4 for PL at equivalent spatial resolution. The porcine model demonstrated superior ICH detectability for PL. The results support the role of high-quality mobile C-arm CBCT employing advanced reconstruction algorithms for detecting subtle complications in the operating room at lower radiation dose and lower cost than intraoperative CT scanners and/or fixed-room C-arms. Such capability could present a potentially valuable aid to patient safety and QA.