Aim: The purpose was to evaluate the general incidence of post-operative pain and flare-ups in patients who were endodontically treated by two endodontics specialists using rotary instruments with the same treatment protocol. Methods: Records of 382 teeth belonging to 268 patients treated by two endodontics specialists during a 6-month period were kept and evaluated. Post-operative pain between treatment visits was categorized using a pre-established scoring system. Ninety-five patients were males, whereas 173 were females. Results: Pulpal necrosis without periapical pathosis was determined as the most common indication for endodontic treatment (21.7%) followed by irreversible pulpitis and re-treatment without periapical lesions (18.3%, 18.3%, respectively). The general prevalence of postoperative pain and flare-ups was determined as 8.1%, whereas cases that could be classified as real flare-ups which were severe and required an unscheduled visit (scores 2 and 3) comprised 3.4% of the cases. No statistically significant correlation was determined between gender and post-operative pain and flare-up (p = 0.05). Conclusion: Teeth with pre-operative pain were more prone to developing post-operative pain and discomfort with a statistically significant difference (p = 0.02). While no significant correlation was determined between tooth vitality and pain and flare-ups (p = 0.5), a statistically significant relationship existed between the presence of a periapicalpathosis and postoperative pain and flare-ups. Cases with a periapical lesion had a higher risk of developing pain and flare-upscompared to those with no periapical involvement (p = 0.0001). Future studies may focus on the influence of rotary instrumentation systems in more specific groups of cases. Meanwhile; microbiological as well as psychological aspects of flare-ups are topics that warrant further investigation.