The aim of this study was to determine the prevalence and severity of cornea guttata (CG) in grafts after Descemet membrane endothelial keratoplasty (DMEK) and to investigate its impact on various clinical parameters during follow-up. This retrospective study included 664 operations (DMEK and triple-DMEK) on 466 patients. The prevalence and progression of CG after the operation were examined using endothelial specular microscopy images. The severity grade of CG was classified into four grades: G0 without CG, G1 - G3 with increasing severity of CG. Clinical parameters such as central corneal thickness (CCT), visual acuity (VA), endothelial cell density (ECD), pleomorphism and polymegalism were examined during a postoperative follow-up time of 19.6 ± 15.8 months. Cornea guttata (CG) appeared postoperatively in 124 (18.7%) eyes. 112 (16.9%) could be classified as G1, 9 (1.4%) as G2 and only 3 (0.5%) as G3. The examination of clinical parameters showed significant differences between healthy and low-grade CG (G0/G1) and high-grade CG (G2/G3). A significant deterioration was found in the corrected distance visual acuity (CDVA) (p = 0.02). CCT showed an increase between G0 (534 ± 58 μm) and G2 (549 ± 71 μm)/G3 (558 ± 56 μm) with a p-value of 0.02. Additionally, a significant increase in pleomorphism (p = 0.003) and polymegalism (p = 0.04) was detected. Cornea guttata (CG) prevalence after DMEK and triple-DMEK was found to be 18.7%, although most of these cases were classified as low-grade CG and showed no clinical significance. Around 1.9% were classified as high-grade CG and significantly affected several clinical parameters during the follow-up.