Objective: Laparoendoscopic single-site myomectomy (LESS-M) is widely applied for the treatment of uterine leiomyoma. The purposes of this study were to investigate differences in hidden blood loss between LESS-M and conventional laparoscopic myomectomy (CLM) during treatment of uterine leiomyoma and to identify the associated risk factors. Design: This is a retrospective study. Participants: The participants of this study were patients who underwent laparoscopic myomectomy (114 and 156 for LESS-M and CLM, respectively) between July 1, 2019, and October 10, 2020, at the Second Affiliated Hospital of Wenzhou Medical University. Setting: The study was conducted at the Second Affiliated Hospital of Wenzhou Medical University. Methods: We enrolled a total of 114 and 156 patients who were treated with LESS-M and CLM, respectively, between July 1, 2019, and October 10, 2020. We collected clinical data, then applied the Nadler and Gross formula and multiple linear regression analysis to calculate the HBL and identify the associated risk factors, respectively. Results: Patients in the LESS-M group had a VBL of 115.4 ± 180.6 mL and an HBL of 364.3 ± 252.6 mL, accounting for 74.4 ± 22.4% of true TBL. On the other hand, patients in the CLM group had VBL of 187.9 ± 198.5 mL, and HBL of 306.8 ± 304.7 mL, accounting for 58.9 ± 30.2% of true TBL. HBL was significantly higher in the LESS-M than the CLM group (p = 0.000). Limitations: This study was the small sample size used. Conclusions: HBL accounted for a significant percentage of TBL in laparoscopic myomectomy, especially in patients treated with LESS-M. Paying attention to perioperative blood changes coupled with fully understanding HBL might promote postoperative recovery of patients.