Objectives: The transphenoidal bi-nostril endoscopic resection of pituitary adenomas is regarded as a minimally invasive treatment nowadays. However, sino-nasal outcome and health-related quality of life (HRQoL) might still be impaired after the adenomectomy, depending on patients’ prior medical history and health status. A systematic postoperative comparison is required to assess differences in perceived sino-nasal outcome and HRQoL. Methods: In this single-center observational study, we collected data from 81 patients, operated between August 2016 and August 2021, at a 3–6-month follow-up after adenomectomy. We employed the sino-nasal outcome test for neurosurgery (SNOT-NC) and the HRQoL inventory Short Form (SF)-36 to compare sino-nasal and HRQoL outcome in patients with or without allergies, previous nose surgeries, presence of pain, snoring, sleep apnea, usage of continuous positive airway pressure (cpap), and nose drop usage. Results: At the 3–6-month follow-up, patients with previous nasal surgery showed overall reduced subjective sino-nasal health, increased nasal and ear/head discomfort, increased visual impairment, and decreased psychological HRQoL (all p ≤ 0.026) after pituitary adenomectomy. Patients with pain before surgery showed a trend-level aggravated physical HRQoL (p = 0.084). Conclusion: Our data show that patients with previous nasal surgery have an increased risk of an aggravated sino-nasal and HRQoL outcome after pituitary adenomectomy. These patients should be thoroughly informed about potential consequences to induce realistic patient expectations. Moreover, the study shows that patients with moderately severe allergies, snoring, and sleep apnea (± cpap) usually do not have to expect a worsened sino-nasal health and HRQoL outcome.