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Abstract Background Immunosuppression (IS) protocols should be individualized according to the individual recipient's immunity to minimize adverse effects. The aim of this study was to determine whether preoperative levels of CD8+ T lymphocytes could be used as a guide for the introduction of IS. Methods Sixteen adult liver transplantations in our institute were retrospectively analyzed. The immunosuppressive agents were temporarily withheld for 8 patients with a lower (<10%) preoperative percentage of CD8+ cells after transplant (classified as group A). In this group, postoperative immunosuppressive agents had never been used until acute rejection was suspected. Another 8 patients receiving classic IS were classified as group B. We collected their demographic features and analyzed the clinical courses. Results The postoperative IS-free period of group A was 5 to 120 days (median, 31 days). Our data showed an inverse correlation between CD8+ levels and the severity of liver disease. Although the IS-free protocol did not present a lower incidence of infection-related events, most of them were effectively treated with antibiotics. The 1-, 3-, and 5-year overall patient survival rates were not different between those with a short-term IS-free period and those with regular IS (87.5% vs 100%, 75% vs 100%, and 62.5% vs 87.5%; P = .468). No patient died of graft failure due to acute rejection. Conclusions Postoperative immunosuppressive agents can be safely withheld for a period of time to preserve proper immune responses against infections in very sick recipients guided by using the CD8+ levels.