Optimal patient positioning for spine surgery is vital for surgical success and the minimization of complications intra-/postoperatively. In patients with complex comorbidities, commercially available surgical positioning equipment is inadequate. To overcome this, a novel method was developed to create custom-fit patient-specific theater mattresses for patients undergoing spine surgery. An innovative digital workflow involving three-dimensional (3D) surface scanning, 3D simulation, and computer-aided design was developed to manufacture customized theater supports with patient-specific requirements. These supports offered the surgeon an enhanced ability to relieve load bearing on prominent anatomical features or where desired, to tailor the support surface to the patient's anatomy for lengthy surgery. The bespoke theater mattress was evaluated by whether the support resulted in a complication-free surgery. Using this new workflow, case examples for two patients with complex comorbidities were described. The spine surgeon and anesthetist reported the patient-specific custom mattresses were fit as per the required design, provided sufficient clearance around anatomical prominences and areas that required to be unloaded, had sufficient clearance for the anesthetic method and cannulation, provided excellent surgical access and stability during surgery, and postoperatively no soft tissue overload over bony prominence and implanted devices. Positive patient outcomes after successful lengthy surgical interventions were associated with these patient-specific, contoured mattress supports. Future projects will seek to utilize this technology for other types of surgeries and intra-operative positioning requirements, and for a broader demographic of patients in both the pediatric and adult setting.