Objectives: Existing knowledge on Health Related Quality of Life (HRQoL) after surgical removal of sinonasal inverted papilloma (IP) is limited. Moreover, predictors for a better or worse postoperative HRQoL outcome are not known. Our aim was to assess HRQoL in all three health domains (physical, psychological and social), track its postoperative trajectory, investigate if preoperative observations could predict distinct postoperative HRQoL outcomes, and evaluate whether physicians’ interventions could contribute to improved postoperative HRQoL. Design: Prospective cohort study. Setting: Tertiary referral hospital. Participants: Seventy-four patients who underwent surgery for an IP were included. They were asked to fill in the Endonasal Endoscopic Sinus and Skull Base Surgery Questionnaire (EES-Q) preoperatively, and then two weeks, three months, and one year postoperatively. Main outcome measures: Linear mixed models (LMM) analyses were performed to evaluate the overall postoperative HRQoL and the separate health domains, as well as the impact of specific variables (sex, age, ASA classification, smoker, Krouse staging, preoperative EES-Q score, type of surgery and postoperative antibiotics) on HRQoL improvement. Results: The total EES-Q score (P<.001) as well as the physical (P<.001), psychological (P=.049), and the social (P=.002) domains significantly improved postoperatively. ASA classification (P=.049), preoperative EES-Q score (P<.001) and postoperative antibiotics (P=.036) were significant variables. Conclusions: Overall HRQoL, as well as each of the three health domains, improved significantly. A higher ASA score, a higher preoperative EES-Q score, and the administration of postoperative antibiotics were significant predictors for better HRQoL recovery postoperatively. Further research is necessary to confirm these results.