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To analyze factors that may lead to inadvertent subretinal retention of perfluorocarbon liquid (PFCL) after vitreoretinal surgery and compare surgical outcomes and complications associated with these events.Consecutive retrospective study.The authors retrospectively reviewed the charts of 72 vitreoretinal surgeries using intraoperative PFCL and its removal through fluid–air exchange and subsequent tamponade. Indications for surgery included trauma, retinal detachment, giant retinal tear, and submacular hemorrhage. Most interventions studied had significant amounts of proliferative vitreoretinopathy and were required after failed or complicated previous vitreoretinal surgery.Analysis was focused on the occurrence of subretinal retention of PFCL during different surgical procedures and techniques, indications, anatomic and visual results, and complications.At the last follow-up, the retina was completely attached in 97% of eyes treated with PFCL after 1 or 2 vitrectomies. Subretinal PFCL was found in 8 (11.1%) eyes. There was no statistical difference in the retention rate for perfluorodecalin and perfluoro-n-octane. The factor most significantly associated with subretinal retention of PFCL was the presence and large size of a peripheral retinotomy. All cases of subretinal PFCL had a retinotomy of 120° or larger. The average retinotomy size in these cases was 259°. Subretinal PFCL was found in 40% of eyes with a 360° retinotomy. Small and medium-sized retinal breaks were not associated with PFCL retention. Another surgical procedure that correlated significantly with subretinal PFCL was lack of saline rinse during fluid–air exchange. Only 1 of the 23 eyes that were rinsed had subretinal PFCL, although many had large retinotomies.Subretinal PFCL retention is most likely to occur in eyes with large peripheral retinotomies, especially if 360°. Saline rinse seems to be useful in the prevention of subretinal PFCL. The presence of subretinal PFCL does not seem to affect visual and anatomic success when located outside the macula, at least during an intermediate period of follow-up.