Endoscopic surgery requires skilled bimanual use of complex instruments that extend the peri-personal workspace. To delineate brain structures involved in learning such surgical skills, 48 medical students without surgical experience were randomly assigned to five training sessions on a virtual-reality endoscopy simulator or to a non-training group. Brain activity was probed with functional MRI while participants performed endoscopic tasks. Repeated task performance in the scanner was sufficient to enhance task-related activity in left ventral premotor cortex (PMv) and the anterior Intraparietal Sulcus (aIPS). Simulator training induced additional increases in task-related activation in right PMv and aIPS and reduced effective connectivity from left to right PMv. Skill improvement after training scaled with stronger task-related activation of the lateral left primary motor hand area (M1-HAND). The results suggest that a bilateral fronto-parietal grasping network and left M1-HAND are engaged in bimanual learning of tool-based manipulations in an extended peri-personal space.