Objectives/Hypothesis: The aims were to determine health-related quality of life (HRQoL), including voice problems, dysphagia, depression, and anxiety after total laryngectomy (TL), and investigate the associations between HRQoL and the late effects. Study Design: Cross-sectional study. Methods: 172 participants having received a TL 1.6 to 18.1 years ago for laryngeal/hypopharyngeal cancer filled in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Core and Head and Neck module (EORTC QLQ-C30, EORTC QLQ-H&N35), Voice-Related Quality of Life questionnaire (V-RQOL), M.D. Anderson Dysphagia Inventory (MDADI), and Hospital Anxiety and Depression Scale (HADS) questionnaires. Results: Participants scored worse than normative reference populations on all scales/items of the EORTC questionnaires, except one, and almost half of the scales/items showed a clinically relevant difference. Moderate/severe dysphagia was present in 46%, moderate/severe voice problems in 57%, depression in 16%, and anxiety in 20%. Decreasing age, increasing numbers of comorbidities, increasing voice problems, increasing dysphagia, and increasing depression symptoms, were associated with a lowered EORTC QLQ-C30 summary score. Conclusion: A substantial proportion of participants experienced clinically significant late effects and increasing levels of these were associated with a lowered HRQoL. Level of Evidence: 3 Laryngoscope, 2021.