Objectives: This study aimed to assess prospectively the clinical outcome of nonsurgical endodontic treatment and identify patient-and tooth-related factors, rather than treatment-related factors, that were the best predictors of this outcome. Materials and Methods: The inception cohort comprised 441 teeth (320 patients) and 175 teeth (123 patients) were followed up for 1-2 years. Age, gender, presence of medical disease, number of canals, previous endodontic treatment, presence of sensitivity and pain, pulp vitality, swelling or sinus tract of pulpal origin on the gingiva, periapical radiolucency and tendency of unilateral bite on the affected tooth were recorded at treatment start. Results: The outcome was classified on the basis of periapical radiolucency as healed or non healed. The overall healed rate in these cases, including nonsurgical retreatment, was 81.1%. Four tooth-related factors had a negative impact in the bivariate analysis: previous endodontic treatment, necrotic pulp, preoperative gingival swelling or sinus tract of pulpal origin, and preoperative periapical radiolucency. Stepwise logistic regression analysis including patient-, tooth-related factors and level of the root canal filling as a treatment-related factor showed that preoperative gingival lesion (odds ratio [OR]: 4.4; p = 0.005), preoperative periapical radiolucency (OR: 3.6; p = 0.011), and ≤ 1-2 mm under root filling length (OR: 9.6; p = 0.012) were significant predictors of failure. Conclusions: A preoperative gingival lesion of pulpal origin can influence the outcome of nonsurgical endodontic treatment in addition to preoperative periapical radiolucency. [J Kor Acad Cons Dent 2010; 35(6):436-444.]