Identifying posterior teeth that are at heightened risk of developing cusp fracture is an inexact science. Risk indicators based on controlled observations are not available, and dentists' assessments vary.The authors conducted a case-control study of cusp fracture in restored posterior teeth. They evaluated 39 potential risk indicators identified in previous uncontrolled studies for an association with fracture in 200 patients with fractures and 252 patients without fractures. These risk indicators delineated patients' clinical characteristics and behaviors, as well as clinical characteristics of individual teeth. The authors used logistic regression to develop models identifying risk indicators associated with fracture, both between case and control subjects and between case and comparison teeth in case subjects.Two risk indicators appeared in both models. The presence of a fracture line and an increase in the proportion of the volume of the natural tooth crown occupied by the restoration substantially increased the odds of fracture (P < .001). Additional risk indicators were unique to the case subject-control subject model, including subject age and other measures related to the relative size of the restoration or to loss of dentinal support. Neither patient behaviors such as clenching, grinding and biting hard objects nor occlusal characteristics such as guidance, cusp anatomy and general wear patterns were strong predictors of fracture risk.Among posterior teeth with restorations, two clinical features were strongly associated with the risk of cusp fracture: presence of a fracture line in the enamel and proportional volume of the restoration.Dentists assessing the risk of fracture should consider a detectable fracture line or a high ratio of restoration-to-total-crown volume as important indicators of elevated risk.