Objectives: This ongoing prospective study evaluates the clinical performance of an ORMOCER restorative material (Definite; Degussa) in combination with a self-conditioning adhesive (Etch & Prime 3.0; Degussa). Method and Materials: Three hundred fifty-six restorations (48 Class I, 150 Class II, 63 Class III, 32 Class IV, and 63 Class V) in 117 patients (17 to 65 years) were placed by 5 operators at 5 centers. Fillings were placed with cotton roll isolation using clear matrix bands for Classes III and IV and metal matrix bands for Class II restorations. Follow-ups took place after 6, 12, and 24 months whereby modified Ryge criteria were recorded. With 33 randomly selected Class I and II restorations, measurements of occlusal wear (3-dimensional laser scanner) and marginal analyses (scanning electron microscope) were done using replicas. Results: At 24 months, 307 restorations were available for evaluation. The cumulative number of losses in the 5 cavity classes (I, II, III, IV, and V) and the percentages of scores for the clinical parameters in the 4 categories (Alfa, Beta, Charlie, and Delta) of the retained restorations were loss (1/ 6/ -/ 2/ 7), marginal integrity (93.1/ 6.9/-/-), marginal discoloration (73.5/ 25.5/ 1/ -), anatomic form (82.8/17.2/-/-), and fracture (93.1/ 6.9/-/ -). Marginal analysis showed 48.7% "continuous margin" initially and 13.2% at 24 months (difference statistically significant, a = 0.05). Occlusal wear at 24 months was 12.3 µm for premolars and 21.4 µm for molars. Conclusions: The overall clinical performance of the ORMOCER restorative over 24 months was acceptable with concerns related to marginal quality and to retention of Class V restorations. Keywords: clinical trial, resin composite, restorative material, self-etching dental adhesive