Aim: Flare-ups following a root canal treatment are still a major problem both to the patient and to the clinician. Its definition, etiology, incidence, and risk factors have been the subject of long-standing debate. We conducted this study to investigate the incidence of flare-ups after a single-visit treatment and to identify the factors associated with the flare-up index (FUI). Materials and methods: All patients treated by postgraduate residents in endodontic specialty at Saint Joseph University of Beirut from June 2018 to January 2019 were invited to participate in the study. After a routine root canal treatment, patients were given a questionnaire to fill after 24 hours–48 hours–7 days, covering a postoperative assessment of symptoms using the visual analogue scale (VAS) and FUI. Patients who experienced a severe postoperative pain and/or swelling were identified and categorized as having a flare-up. Results: A total of 423 patients (age: 39.76 ± 12.428 years) were included in the study. The incidence of flare-up was 1.9%. The mean FUI was 5.94 ± 5.646 and was highly correlated with the VAS score (p < 0.001). The factors that significantly influenced the occurrence of flare-ups were: pulpal diagnosis (p < 0.001), preoperative drug intake (p < 0.001), preoperative symptoms (>24 hours) before treatment (p < 0.001), and tooth type (p = 0.013). Conclusion: FUI should be used in further studies to confirm our results since it is a valid quantitative method to assess this clinical phenomenon. Clinical relevance: Endodontists should take into consideration the diagnosis and the history of preoperative symptoms since it plays an important role in predicting the occurrence of flare-ups and the success of the treatment.