(1) Background: The goal of this study is to evaluate psychological tolerance and health-related quality of life (QOL) in head and neck (HN) cancer patients treated with definitive accelerated radiotherapy (DART). (2) Methods: 76 recurrence-free patients eligible for the study, who were treated with DART in the CAIR-2 phase III clinical study (median of follow-up = 47 months), completed EORTC QLQ-C30 with the H&N35 module, Hospital Anxiety and Depression Scale (HADS) and Visual-Analog Scales (VAS) of pain in HN and the neck/arm areas. (3) Results: The most dominant symptoms measured with QLQ-C30 were as follows: fatigue (44/100), sleeplessness (39/100), financial problems (38/100) and pain (32/100). Within the H&N35, the highest scores were reported on the subscales of sticky saliva (60/100), mouth dryness (65/100) and increased intake of painkillers (50/100). Pain (VAS) was reported by 87% (HN area) and 78% (shoulder area) of the patients, with a mean score of 3/10. One-third of the patients reported depressive moods (HADS ≥ 15 points) with an average score of 12.5/42 p. The depressed group, who smoked more as compared to the non-depressed group before DART (96% vs. 78%) and required steroids treatment (85% vs. 58%) during DART, also scored significantly worse on 23 of the 35 subscales of QLQ-C30 and H&N35 and experienced more intense pain (VAS). Women and less-advanced patients scored better in several aspects of quality of life. (4) Conclusions: Patients treated with DART struggle with low quality of life and persistent treatment-related symptoms including constant pain. HNC survivors, especially those who are depressed, may require additional psychosocial, rehabilitation and medical intervention programmes.