Objectives: To analyze postoperative clinical, functional, and quality-of-life (QOL) outcomes in patients after total laryngectomy (TL) and to determine the effect of preoperative variables (including age, sex, comorbidities, prior chemotherapy or radiation therapy, and tumor site and stage) on long-term survival and quality of life. Design: We performed a retrospective cohort follow-up study of patients who underwent TL for cancer between July 28, 1994, and August 11, 2005. Setting: University tertiary care facility. Patients: One hundred forty-three patients who underwent TL were identified, and their hospital medical records were reviewed. Ninety-one patients (63.6%) underwent TL for primary carcinoma and 52 (36.4%) for recurrent cancer. At follow-up, 58 patients (40.6%) were alive. Main Outcome Measures: Baseline characteristics and preoperative clinical variables were collected. Follow-up data on function and QOL were collected from patients who were alive at the time of study via the Head and Neck Cancer Inventory, a previously validated questionnaire. Survival was estimated using the KaplanMeier method. Univariate and multivariate analysis was used to determine factors significant for survival. Results: The overall median survival for the cohort was 23.0 months (mean SD, 50 29 months). On univariate analysis, the following 5 factors were significant predictors of long-term survival: cancer site in the larynx, T3 stage, N0 to N1 stage, presence of no more than 2 comorbidities, and absence of cardiovascular comorbidities at the time of cancer diagnosis (P <.05). On multi-variate analysis, only T stage maintained significance as a predictor of survival (P =. 04), while cancer site was nonsignificant at P=.07. For patients alive at the time of study, functional and QOL outcomes for 5 domains (speech, eating, social disruption, aesthetics, and overall QOL) ranged from intermediate (score, 31-69) to high (score, 70100) categories. Pretreatment patient-related factors that correlated with notably better functional and QOL outcomes in at least 1 domain were age older than 65 years at diagnosis, presence of no more than 2 comorbidities, no history of previous chemoradiation therapy, and primary tracheoesophageal puncture placement. Conclusions: Pretreatment clinical variables (including primary tumor site, tumor stage, regional metastases, and number and type of comorbidities) have an effect on long-term survival after TL. Despite common belief, many patients who have undergone TL maintain a good QOL overall. This study sheds light on which patient-related factors may affect health-related QOL outcomes after TL. These findings may be used to select patients who are good candidates for TL based on anticipated functional and QOL outcomes.