Objective: The aim of the study was to compare the extent of tissue trauma after abdominal hysterectomy(AH), vaginal hysterectomy (VH), and total laparoscopic hysterectomy (TLH) using biochemical markers. Material and methods: Seventy-one patients requiring hysterectomy for benign uterine diseases were enrolled in the study and divided into three treatment groups: AH (n=24), VH (n=23), and TLH (n=24). Blood samples for assay of interleukin-6 (IL-6) and creatine phosphokinase (CPK) were collected pre-, intra-operatively, and 2, 6 and 24 h after surgery. Results: Serum levels of IL-6, and CPK were significantly elevated over basal values after surgery in all groups. IL-6 and CPK levels were significantly higher after AH as compared to VH and TLH. IL-6 concentrations were significantly higher in the VH group than the TLH group (p=0.001). There were no significant differences in CPK levels between the VH and TLH groups (p=0.824). TLH group had the smallest decrease in blood hemoglobin concentration and the shortest hospital stay. Conclusions: AH causes more tissue trauma as compared to VH and TLH. Owing to the fact that TLH is associated with less tissue trauma and offers significant clinical benefits, including less blood loss and shorter hospital stay, it should be considered in women with benign gynecologic conditions, especially in experienced centers.