Anesthesia for aorta surgery in pigs remains challenging due to the requirements for mechanical ventilation and the need for maintaining adequate homeostasis. We report an improved anesthesia protocol in an in vivo animal model to test a novel bacterial nanocellulose (BNC) within the ‘Kardio-BNC’ trial. Forty-four 6-month-old DanBred pigs comprising 6 males and 38 females (body weight ca. 82 kg) underwent implantation of pericardium reconstructive patches (n = 8), thoracic aorta prostheses (n = 15), or both procedures (n = 17) to test the biocompatibility of the novel BNC. The primary endpoint was 90-day survival, and the secondary outcome was death for any reason before reaching the study endpoint. Univariate analysis and linear regression were used to identify variables associated with premature mortality. Of the 44 pigs that underwent surgery, 10 (23%) were lost intra-operatively because of arrhythmia (n = 1), anesthesiological causes (n = 4), or surgical complications (n = 5). Modifications to tracheal intubation, tube fixation, temperature maintenance, and vascular catheterization increased the survival rate to 91% in the last quartile of the animals that underwent surgery. Of the 34 animals that survived surgery, n = 10 (29%) were lost post-operatively because of hematoma (n = 2), pneumothorax (n = 1), or infection (n = 7). Infection was associated with the type of surgery (highest prevalence in animals undergoing the combined procedure; p = 0.02), azaperone dose (p = 0.03), intra-operative heart rate variability (p = 0.03), and crystalloid transfusion (p = 0.04). The anesthesiological strategies and modifications to surgery described here allowed safe open chest and aorta surgery in up to 91% of the procedures performed