The superiority of distinct anesthesia methods for geriatric hip fracture surgery remains unclear. We evaluated high mobility group box-1 (HMGB1) and interleukin-6 (IL-6) with three different anesthesia methods in elderly patients undergoing hip fracture surgery. Routine blood test findings, postoperative morbidity, and mortality were assessed as secondary outcome. In total, 176 patients were randomized into desflurane (n = 60), propofol (n = 58), or spinal groups (n = 58) that received desflurane-based balanced anesthesia, propofol-based total intravenous anesthesia (TIVA), or spinal anesthesia, respectively. The spinal group required less intraoperative vasopressors (p < 0.001) and fluids (p = 0.006). No significant differences in HMGB1 (p_group×time = 0.863) or IL-6 (p_group×time = 0.575) levels were noted at baseline, postoperative day (POD) 1, or POD2. Hemoglobin, albumin, creatinine, total lymphocyte count, potassium, troponin T, and C-reactive protein were comparable among groups at all time-points. No significant differences in postoperative hospital stay, intensive care unit (ICU) stay, and ventilator use among groups were observed. Postoperative pulmonary, cardiac, and neurologic complications; and in-hospital, 30-day, and 90-day mortality were not significantly different among groups (p = 0.974). In conclusion, HMGB1 and IL-6, and all secondary outcomes, were not significantly different between desflurane anesthesia, propofol TIVA, and spinal anesthesia.