OBJECTIVE To evaluate prospectively the longevity of ceramic inlay/onlay restorations placed in a web-based practice-based research network and to investigate risk factors associated with restoration failures. MATERIALS AND METHODS Data were collected by a practice-based research network called Ceramic Success Analysis (CSA). 5791 inlay/onlay ceramic restorations were placed in 5523 patients by 167 dentists between 1994 and 2014 in their dental practices. For each restoration specific information related to the tooth, procedures and materials used were recorded. Annual failure rates (AFRs) were calculated and variables associated with failure were assessed by a multivariate Cox-regression analysis with shared frailty. RESULTS The mean observation time was 3 years (maximum 15 years) of clinical service, and AFRs at 3 and 10 years follow up were calculated as 1.0% and 1.6%. Restorations with cervical outline in dentin showed a 78% higher risk for failure compared to restorations with margins in enamel. The presence of a liner or base of glass-ionomer cement resulted in a risk for failure twice as large as that of restorations without liner or base material. Restorations performed with simplified adhesive systems (2-step etch-and-rinse and 1-step self-etch) presented a risk of failure 142% higher than restorations performed with adhesives with bonding resin as a separate step (3-step etch-and-rinse and 2-step self-etch). 220 failures were recorded and the most predominant reason for failure was fracture of the restoration or tooth (44.5%). CONCLUSIONS Ceramic inlay/onlay restorations made from several glass ceramic materials and applied by a large number of dentists showed a good survival. Deep cervical cavity outline, presence of a glass ionomer lining cement, and use of simplified adhesive systems were risk factors for survival.