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Purpose: Laparoendoscopic single-site surgery has recently been described in children and regarded as an improved technology leading to less pain and better cosmetic outcome. Compared to the traditional three-port method, it is not known if the single-port method is less invasive. The aim of this study was thus to investigate the post-operative acute inflammatory response in order to evaluate surgical stress in the two surgical approaches in children.Methods: A prospective, single blinded, case-control study was carried out. Thirteen male patients who presented with unilateral varicocele were divided into two groups. Six children underwent single-port laparoscopic procedure, while the other seven children underwent three-port laparoscopic procedure. Pre-operative and post-operative blood samples were taken for the measurement of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) using ELISA. Demographics including the operation time, and complications were recorded. Data between the two groups were analyzed using unpaired t-test and a p value of <0.05 was taken as statistically significant.Results: The mean age of patients was 14.5 years (range 12-19 years). There was no significant difference between the two groups in terms of operative time, nor there was any complication recorded. The change in serum TNF-α and IL-6 concentrations pre- and post-operatively between the single-port group and three-port group was not statistically significant. Overall, patients in the two groups showed excellent satisfaction in terms of post-operative cosmesis.Conclusion: Single-port laparoscopic varicocelectomy is safe, effective and produces excellent cosmesis with minimal surgical stress. [ABSTRACT FROM AUTHOR]