The objective of this study was to compare health-related quality of life (HRQOL) after sequential cholesteatoma surgery including exclusively transcanal technique (ETC), combined transcanal transmastoidal technique (TCM) and canal wall down surgery with obliteration (CWD). It was a clinical case study conducted in a tertiary referral center. 97 patients at least 12 months after cholesteatoma surgery were included. Interventions included sequential cholesteatoma surgery with ETC, TCM or CWD; ossiculoplasty with partial and total ossicular replacement prostheses. HRQOL assessed by Chronic Otitis Media Outcome Test 15 including an overall score and three subscores ('ear symptoms', 'hearing function' and 'mental health') as well as a general evaluation of HRQOL and the frequency of physician consultations, audiometric outcome related to HRQOL were the main outcome measures. Patients, who had undergone sequential cholesteatoma surgery, showed moderate restrictions in HRQOL postoperatively. Stratified for the three surgical techniques, patients receiving ETC tended to report lower restrictions in HRQOL. The ETC group offered a significantly lower value in the subscore 'ear symptoms'. The 'hearing function' was attributed to be the most restriction criteria for all techniques. The overall score and all subscores correlated moderately with the postoperative air conduction threshold. The strongest correlation coefficient was achieved for the subscore 'hearing function' (r(s) = 0.49, p < 0.001). Sequential cholesteatoma surgery offers acceptable moderate restrictions in HRQOL postoperatively. Patients receiving canal wall down surgery with obliteration showed equivalent limitations in HRQOL compared to closed techniques (ETC, TCM). The postoperative air conduction threshold was shown not to be a sufficient indicator for HRQOL. Therefore, disease-specific validated and reliable measuring instruments for HRQOL should be transferred from clinical research to clinical practice to provide an individualized postoperative assessment after cholesteatoma surgery.