For women who desire pregnancy or who wish to retain their uterus, myomectomy is the standard approach for the treatment of fibroids. Abdominal myomectomy seems to be the best choice when there are large subserosal or intramural fibroids (>5-7 cm), or submucosal fibroids >3 cm or when multiple fibroids (>3) are to be removed. When submucosal myomas are present or multiple fibroids are to be removed, opening the uterine cavity during the surgical procedure is more likely to happen. There is lack of published evidence about whether there is any difference in perioperative morbidity and management of those cases where the uterine cavity is opened during the surgical procedure compared with those where the uterine cavity remains closed. Methods: We undertook a retrospective review of 423 abdominal myomectomies via either an opened or closed uterine cavity. As a primary outcome we assessed the overall perioperative morbidity rate and as a secondary outcome we compared the necessity of pre and postoperative transfusions, intraoperative bleeding, febrile morbidity, unintended surgical interventions, life-threatening events, need for relaparotomies and duration of hospital stay between the opened and non opened uterine cavity groups. Results: The overall perioperative morbidity rate was significantly higher in those cases where the uterine cavity was opened during surgery; however the difference was caused only by the increased risk of intraoperative bleeding. All the other variables, such as febrile morbidity, number of relaparotomies, unintended surgical procedures and life-threatening events did not differ between the two groups. Conclusion: Although there is an increased risk of intraoperative bleeding it seems that entering the uterine cavity during abdominal myomectomy can be considered as safe a procedure as in those cases where the uterine cavity remains closed.