Background/purpose To report on health-related quality-of-life (HRQoL) of patients with laryngeal cancer, treated in a randomized trial comparing accelerated radiotherapy with carbogen and nicotinamide (ARCON) against accelerated radiotherapy alone (AR). Material/methods HRQoL was assessed using the HRQoL Questionnaire-C30 (QLQ-C30) and the Head & Neck cancer module (QLQ-H&N35) at baseline, at completion of radiotherapy and at 6, 12, and 24 months post-baseline. Results From 269/345 patients (AR: 136/174; ARCON: 133/171) data on HRQoL were available for analysis. Moderate to severe clinical impact of the treatment was observed for nearly all items of the QLQ-C30 and QLQ-H&N35 between baseline and end-of-treatment. At 6 months, scores returned to baseline level with exception of dry mouth, sticky saliva, and taste/smell. No difference between AR and ARCON was observed. At 2 years from baseline, the percentage of patients reporting moderate to severe complaints of dry mouth, sticky saliva, or changes in taste/smell was 30%, 22% and 18%, respectively, while the majority of patients had no or few complaints of swallowing (79%) or speech (64%). Conclusions With accelerated radiotherapy, high local tumor control was obtained while maintaining good speech and swallowing function. Long-term dry mouth, sticky saliva and changes in taste/smell are limited to one quarter of patients. (ClinicalTrials.gov number, NCT00147732).