Objectives: The aim of the present study was to evaluate the ormocer Definite (Degudent, Hanau, Germany) as resin luting cement. Methods: In a controlled prospective clinical study, 57 Cergogold (Degudent) all-ceramic inlays were placed in 24 patients by four dentists. The restorations were luted with two different systems (MD = Definite Multibond + Definite; SV = Syntac + Variolink Ultra, Ivoclar Vivadent, Liechtenstein) without lining. At baseline, after 12, 24, and 48 months, restorations were examined according to modified USPHS scores and criteria. Results: One patient including three restorations missed the 4 years recall (dropout). After 48 months of clinical service, four restorations in four patients (three luted with Definite, one with Variolink) failed due to inlay fracture (n = 3) and tooth fracture (n = 1), all other fillings were clinically acceptable (survival rate 93.3% for Definite vs. 95.2% for Variolink; Kaplan-Meier algorithm). Except for the rate of hypersensitivity at baseline (MD: 27%; SV 0%; p < 0.05), no differences were evident between the luting cements at any recalls (Mann-Whitney U-test; p > 0.05). Between the four recalls, a statistically significant deterioration was detected for both groups regarding the criteria marginal adaptation, filling integrity (cracks/chippings/fractures), and tooth integrity (Friedman test; p < 0.001). After 4 years, mainly distinct deterioration with marginal fractures or chippings in proximal and marginal areas of the inlays were observed. No differences were found for surface roughness, color matching, and proximal contact (p > 0.05). Conclusions: For luting of ceramic inlays, only slight differences between the two luting systems were detectable.