<b><i>Introduction:</i></b> The aim of this study was to determine whether the use of perfluorocarbon liquid (PFCL) affects the rate of retinal re-attachments after an initial attachment by vitrectomy in eyes with rhegmatogenous retinal detachment (RRD). <b><i>Methods:</i></b> This was a retrospective, observational, multicenter study of 3,446 eyes registered in the Japanese vitreoretinal surgery treatment information database. Of these, 2,648 eyes had undergone vitrectomy as the first surgery for RRD. The re-attachment rates after the primary vitrectomy with or without PFCL were evaluated. In addition, the significance of factors affecting the re-detachments was determined by univariate and multivariate analyses. The measured outcomes were the rates of re-attachments after the primary vitrectomy with or without the use of PFCL. <b><i>Results:</i></b> A total of 2,362 eyes in the database were analyzed: 325 had and 2,037 did not have PFCL injected into the vitreous cavity during the vitrectomy. The rate of re-attachments was 91.5% in the PFCL group and 93.2% in the non-PFCL group (<i>p</i> = 0.46, χ<sup>2</sup> test). Although there were several risk factors associated with the re-detachments in eyes without PFCL (<i>p</i> < 0.05, Welch’s <i>t</i> tests, and Fisher’s exact tests), they were not associated in eyes with PFCL use. However, multivariate analyses showed that there was no significant association between the use and the non-use of PFCL in the rate of re-detachments (β = −0.08, <i>p</i> = 0.46). <b><i>Conclusions:</i></b> The use of PFCL during the initial vitrectomy for RRD does not affect the rate of re-attachments.