Nonfunctioning pituitary adenomas (NFPAs) can be associated with significant morbidity including a compromised quality of life (QoL). Radiotherapy (RT) is listed as one of the contributing factors to QoL impairment in these patients, however the evidence supporting this association is scarce and conflicting. Here we evaluate health-related QoL (HRQoL) impairment in patients with NFPA and to what extent this is due to RT. HRQoL was evaluated with the short form-36 questionnaire (SF-36), which explores 8 domains pertaining physical, emotional, and mental well being. We assessed 50 patients with NFPA subjected to RT after pituitary surgery, and their results were compared to those from 127 subjects who had undergone surgery but not RT. Both groups were matched for age, sex, and metabolic and cardiovascular comorbidities. The SF-36 was applied a median of 72 months after RT in the group of cases and 78 months after the last surgical procedure in the control group. Both groups scored equally low in the 8 areas explored by the survey. In a multiple linear regression model, age was significantly associated with worse physical health scores, whereas female sex was associated with worse general health perception and lower emotional role and physical role scores. The presence of a visual field defect was significantly associated with a worse social role functioning score. QoL in patients with NFPAs is significantly compromised in most scales evaluated by the SF-36 survey. However, RT itself does not affect QoL.