: Laparoscopic and open surgeries have been compared with conflicting results regarding their clinical outcome and systemic responses. The Alterations in serum levels of certain biochemical markers correlate directly with extent of tissue damage and inflammatory reaction. This study compares the intensity of tissue injury by assessing plasma C-reactive protein (CRP), lactic dehydrogenase (LDH), and cortisol in patients undergoing laparoscopic hysterectomy compared to abdominal hysterectomy. This study was conducted at Ain Shams University Maternity Hospital from May 2018 to February 2020. 80 women candidates for hysterectomy were recruited and randomized into two groups; group (A) included 40 cases who underwent abdominal hysterectomy, and group (B): included 40 cases that underwent laparoscopic hysterectomy. laparoscopic hysterectomy group has a significantly better postoperative recovery compared to the laparotomy group. However, the mean operation time was longer, but the duration of hospital stay was shorter and postoperative Hb drop was lower in the laparoscopy group compared with the laparotomy group. Regarding inflammatory response and tissue damage, CRP and LDH significantly increased postoperatively in both groups. Postoperative mean serum CRP and LDH were significantly higher in the laparotomy group (11.62±4.32, 272.21±76.67 respectively) compared to laparoscopy group (8.12±3.25, 153.53±40.46) (p<0.05). There were no significant differences in cortisol level. TLH is associated with less tissue trauma as assessed by lower postoperative CRP and LDH values, it also 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..