Purpose To establish the frequency and the risk factors for iatrogenic retinal breaks during three-port pars plana vitrectomy (PPV). Methods A total of 2471 PPV operations were included in the study. The study period was between 2001 and 2010, all the data were entered in an electronic patient record database. All 270 consecutive eyes of 270 patients developing iatrogenic retinal breaks during primary PPV were matched to 270 controls. Univariate and multivariate analysis were performed to establish the risk factors. Results The median age of the patients with iatrogenic breaks was 60.06 years; male to female ratio was 140/130. The overall frequency of iatrogenic retinal breaks was 10.09%. The frequency of iatrogenic retinal breaks for eyes undergoing PPV for tractional retinal detachment (TRD) was 32.45%. The lens status was phakic in 79.6% of the eyes, with iatrogenic breaks compared with 34.4% of the eyes in control group (Po0.001). Posterior vitreous was attached in 58.9% of the eyes with iatrogenic breaks compared with 50.4% of the eyes in control group (P ¼ 0.04). Internal limiting, epiretinal, proliferative, or fibrovascular membrane removing manoeuvers were performed in 71.1% of the eyes with iatrogenic breaks compared with 61.9% of the eyes in control group (P ¼ 0.052). Conclusion Eyes undergoing PPV for TRD had significantly higher frequency of iatrogenic retinal breaks compared with other subgroups (P ¼ 0.0001). Phakia and absence of PVD were found to be risk factors for iatrogenic retinal breaks.