Endoscopic surgery may in the future become an attractive alternative to open fetal surgery. Herein, we present our evolving experience with minimal access techniques in sheep and nonhuman primate models. Fifty-two pregnant sheep (term = 145 d) were used. All underwent laparotomy. Cannulas were 5 mm diameter with balloon fixation device. In group I (95-105 d, n = 22, and 70-74 d, n = 19), a total of 119 cannulas were placed by open hysterotomy and pursestring suture through myometrium and membranes. In group II (n = 11), access was obtained by Seldinger guidewire technique. Eight cannulas were introduced over a dilator and 7 were radially expanding endoscopic cannulas. Fifteen cannulas were also placed in 5 pregnant Rhesus monkeys using Seldinger and radially expanding techniques. Cannula removal was followed by insertion of a collagen sponge plug and oversewing of the myometrium. Mini-hysterotomies with purse-stringing provided excellent access to the amniotic cavity, without dissection of the membranes. Classic Seldinger technique with forward dilatation was equally effective, but caused stretching of membranes. In sheep and in primates, Seldinger technique with radial dilatation allowed safe access without membrane separation. Leak-proof removal of the cannulas was achieved in all primates. Open hysterotomy with purse-string and balloon-tipped cannula provides efficient and safe access to the gravid sheep uterus. Seldinger technique allows equally secure access, and alleviates the need for hysterotomies. Radial dilatation of the porthole eliminates forward dissection of the membranes, both in sheep and primate models. This method, and collagen plug insertion upon completion of the endoscopic procedure, may provide a truly minimally invasive approach to in-utero surgery.