The aim of this study was to evaluate the visual, pachymetric, tomographic, and biomicroscopic findings in a series of cases with laser in situ keratomileusis (LASIK) flap interface fluid syndrome (IFS) after Descemet membrane endothelial keratoplasty (DMEK). Six cases were included in this study; all patients had a history of LASIK and underwent DMEK for the treatment of bullous keratopathy. After uneventful surgery, all patients presented with corneal edema and IFS under the LASIK flap, which was demonstrated with anterior segment optical coherence tomography (AS-OCT). Visual acuity, clinical findings, pachymetry, endothelial cell count, and AS-OCT were documented during the management of these cases. IFS appears 2.33 days (±1.03) after DMEK. One case improved with conservative treatment. In 5 cases, the LASIK flap was lifted, the fluid was drained, and the flap was replaced. The mean best-corrected visual acuity after fluid drainage was 0.44 logMAR (range 0.18-1.0) and mean central corneal thickness was 538 μm ± 160. Total resolution of the IFS was achieved at 14.5 days (range 4-30) after DMEK. AS-OCT showed resolution of the flap interface in 5 of 6 cases, while 1 patient required second DMEK due to reaccumulation of the interface fluid. IFS can occur after DMEK in patients with previous LASIK. AS-OCT is a valuable tool for monitoring these cases preoperatively and postoperatively. Early surgical management is often needed to achieve resolution.