© 2021, The Author(s).Objective: To evaluate whether periapical surgery affects oral health-related quality of life (OHRQoL) within the first postoperative week. Study design: The primary outcomes in 133 patients (54 men, 79 women; mean age 50.8 years) undergoing periapical surgery were the Oral Health Impact Profile-14 (OHIP-14) score and postoperative sequelae, including pain, analgesic intake, swelling, limited mouth opening, chewing difficulties, and postoperative infection. Results: We found a significant effect on OHIP-14, pain, and analgesics, which decreased throughout the week. We found no significant differences in mean OHIP-14, pain scores, or analgesic use for gender, medical history, surgical flaps, operation time, or location of the operated teeth. Younger patients had a higher OHIP-14 score in the first 2 days after surgery and more pain on the first postoperative day. Women experienced more pain during the first 3 days. Smokers had a higher OHIP-14 score on the first postoperative day and greater pain during the first 3 days compared to non-smokers. Conclusion: We identified a low incidence of pain and reduced OHRQoL following periapical surgery. The postoperative reduction in OHRQoL and pain were of short duration, with maximum intensity in the early postoperative period and rapidly decreasing with time.