Persistent apical periodontitis related to a nonvital tooth that does not resolve following root canal treatment may be compatible with health and may not require further intervention. This research aimed to develop a Deterioration Risk Score (DRS) to differentiate lesions requiring further intervention from lesions likely to be compatible with health. In this cross-sectional study, patient records (2003-2008) were screened for root-filled teeth with periapical radiolucency visible on periapical radiographs taken at treatment and at recruitment at least 4 yr later. The final sample consisted of 228 lesions in 182 patients. Potential demographic and treatment risk factors were screened against 3 categorical outcomes (improved/unchanged/deteriorated), and a multivariate independent multinomial probit regression model was built. A 5-level DRS was constructed by summing values of adjusted regression coefficients in the model, based on predicted probabilities of deterioration. Most lesions (127, 55.7%) had improved over time, while 32 (14.0%) remained unchanged, and 69 (30.3%) had deteriorated. Significant predictors of deterioration were as follows: time since treatment (relative risk [RR]: 1.11, 95% confidence interval [CI]: 1.01-1.22, p = .030, rounded beta value = 1, for every year increase after 4 yr), current pain (RR: 3.79, 95% CI: 1.48-9.70, p = .005, rounded beta value = 13), sinus tract present (RR: 4.13, 95% CI: 1.11-15.29, p = .034, rounded beta value = 14), and lesion size (RR: 7.20, 95% CI: 3.70-14.02, p < .001, rounded beta value = 20). Persistent apical periodontitis with DRS <15 represented very low risk; 15-20, low risk; 21-30, moderate risk; 31-40, high risk; and >40, very high risk. DRS could help the clinician identify persistent apical periodontitis at low risk for deterioration, and it would not require intervention. When validated, this tool could reduce the risk of overtreatment and contribute toward targeted care and better efficiency in the timely management of disease.