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Objective: The objective of this study was to choose the optimal anesthesia method for gastric cancer patients undergoing surgery with lymph node dissection. Materials and Methods: The study included 53 patients with stage T1-4aN0-3M0 gastric cancer, who underwent radical surgery with xenon and dexmedetomidine (DMM) anesthesia in combination with epidural analgesia (main group, 27 patients) or with sevorflurane anesthesia in combination with epidural analgesia (comparison group, 26 patients). All patients underwent monitoring of hemodynamic parameters, blood coagulation system, thromboelastometry, and inflammation and metabolic parameters (interleukins, hormones and glucose levels), with an assessment of complications according to the Clavien-Dindo classification and the intensity of postoperative pain. Results: Awakening and extubation times, narcotic analgesic consumption, and Numeric Rating Scale pain scores were lower in the xenon + DMM group than in the sevoflurane group (p < 0.05). The overall number of patients experiencing complications did not differ significantly between anesthesia types; however, significant differences were found in the total number of complications (p = 0.003), the number of complications according to Clavien-Dindo I (p = 0.043) and II (p = 0.019), and the incidence of postoperative nausea and vomiting (p = 0.042). Conclusions: The BIS monitoring data obtained showed a sufficient level of anesthesia depth during surgery in both groups; however, post-anesthesia depression persisted longer in patients in sevoflurane group. Mathematical models for predicting Clavien-Dindo IIIb-V complications and severe postoperative pain syndrome are characterized by high sensitivity and specificity. They include simple clinical and laboratory parameters as well as type of anesthesia as predictors. The limitations of predictive models are also discussed in the article.