Post-surgery immunomodulation, including reduced natural killer cell cytotoxicity (NKCC), is recognized as a predictor of poor outcomes in patients following cancer surgery. The present study investigated direct immunomodulation via ketamine as an anesthetic adjuvant in patients undergoing cancer surgery. The present non-double blinded randomized trial was conducted at Hirosaki University Hospital with 60 patients who underwent minimally invasive robotic radical prostatectomy to minimize the immunomodulation due to surgical stress. Patients received total intravenous anesthesia using propofol and remifentanil, with ketamine as an anesthetic adjuvant (the ketamine group) or without ketamine (the control group). The primary outcome was the difference in NKCC between these groups. The secondary outcomes were the differences in neutrophil-lymphocyte ratio (NLR) and levels of interleukin (IL)-6, IL-1ß, IL-10 and tumor necrosis factor-alpha (TNF-α). NKCC and cytokines were measured before anesthesia (baseline) and at 6 and 24 h after baseline measurements were recorded. NLR was determined on the last day before admission and at 48 h post-baseline. NKCC values were similar in each group at 6 h when compared with respective baseline results (baseline control, 36.9±15.6%; 6 h control, 38.3±13.4%; baseline ketamine, 36.1±17.0%; 6 h ketamine, 36.6±16.4%) but significantly decreased at 24 h (control, 26.5±12.2%; ketamine, 24.1±12.7%; P<0.001). There were no significant differences in NKCC between the ketamine and control groups (P=0.64) at any of the assessed time points. NLR, IL-1ß, IL-10 and TNF-α levels were also similar between two groups. In contrast, IL-6 at 24 h was significantly lower in the ketamine group compared with the control group (mean difference, -7.3 pg ml-1; 95% confidence interval, -14.4 to -0.2; P=0.04). Ketamine as an anesthetic adjuvant did not provide direct immunomodulation in patients who underwent cancer surgery.