AIM: To study and compare the effect of different surgical settings on the development of iatrogenic retinal tears (IRT) in conventional (20-gauge) and microincisional vitrectomy. METHODS: An international retrospective comparative study of 394 patients who had simple vitrectomy at three tertiary centers. Surgeries were performed by four retina surgeons using different viewing systems. Two groups of eyes were compared: microincisional vitrectomy (327 eyes) and conventional (67 eyes) vitrectomy. An iatrogenic tear was defined as the occurrence of one or more peripheral retinal tears during surgery or at any visit in the first 6wk postoperatively. RESULTS: Mean age was 67±12y and 55% were female. Iatrogenic tears occurred in 11/394 (2.8%) of eyes. The rate of tears was similar among different surgeons and viewing systems (P=0.93 and P=0.76, respectively). Surgical indication, preexisting pseudophakia/aphakia, induction of posterior vitreous detachment (PVD) during surgery, and the use triamcinolone acetonide didn’t significantly affect the rate of tears (P>0.1 for all factors). A higher rate of tears was found in the conventional group compared to the microincisional group (respectively, 7.5%, 1.8%, P=0.02). CONCLUSION: The rate of IRT in vitrectomy is not significantly affected by surgical indication, preexisting PVD or pseudophakia, or use of triamcinolone or different viewing systems but is significantly higher in conventional vitrectomy. Microincisional platforms improve the safety of vitrectomy regardless of the viewing system used.