The aim of this study was to analyze the long-term outcomes of endodontic microsurgeries in a cohort and identify their association with prognostic factors. A cohort of endodontic microsurgeries followed up periodically with complete clinical and radiographic records for at least 5 years were reviewed retrospectively. Their survival and healing status and profile characteristics were analyzed by Pearson chi-square test and logistic regression (α = 0.05) to identify prognostic factors that influenced outcomes. Of 652 cases in the cohort, 225 (34.5%) were included. The mean follow-up period was 90.4 months (range, 60–168 months). The long-term success rate was 80.5%, and the 5-year survival rate was 83.5%. Logistic regression showed higher success in anteriors compared to molars (OR = 5.405, (95% CI, 1.663–17.571; p = 0.005)) and in teeth with crown restorations (OR = 10.232, (95% CI, 3.374–31.024; p < 0.001)). Conversely, lower success was found in teeth with periodontal disease (OR = 0.170, (95% CI, 0.032–0.900; p = 0.037)) and maxillary sinus involvement (OR = 0.187, (95% CI, 0.035–0.994; p = 0.049)). Endodontic microsurgery has a highly favorable long-term outcome. Tooth position, crown restoration, periodontal disease, and maxillary sinus involvement were identified as main prognostic factors.