To address the efficacy in terms of intraperitoneal spillage of laparoscopically guided minilaparotomy compared with operative laparoscopy for large adnexal cysts. A randomized controlled trial was carried out at a tertiary referral center from January 2005 to September 2006. Sixty eligible patients affected by nonendometriotic adnexal cysts with diameter between 7 and 18 cm were randomly assigned to either operative laparoscopy or laparoscopically guided minilaparotomy. The relative risk for intraperitoneal spillage among women treated with laparoscopy was 5.55 (95% confidence interval 1.88-16.33). Operative times were significantly shorter in patients who underwent laparoscopically guided minilaparotomy. Surgical difficulty was significantly higher in patients treated with laparoscopy. However, postoperative stay was shorter. Laparoscopically guided minilaparotomy, when compared with laparoscopy, is able to reduce intraperitoneal spillage in patients with presumably benign large adnexal masses, with minimal increase in patient short- and long-term discomfort. Because data regarding the importance of intraperitoneal spillage during surgery for benign and malignant pathologies, as well as rupture rates during traditional laparotomy, are scarce, traditional laparotomy still represents the standard treatment. In women desiring a minimally invasive strategy for large cysts, laparoscopically guided minilaparotomy should be considered. Australian Clinical Trials Registry, www.actr.org.au, ACTR N012607000241437, I.