The quality of life (QoL) impact of multidisciplinary treatment for patients with nonfunctioning pituitary macroadenomas (NFPMA) is unclear. We sought to assess patient-reported QoL in our institutional experience using a cross-sectional survey. We identified 488 patients with NFPMA treated at our institution from 1980-2010 who underwent transsphenoidal surgery (TSS) with or without adjuvant salvage therapy with radiation therapy (RT) and/or surgery. The following validated patient-reported outcome measures were collected: the RAND Short Form-36 Health Survey (SF-36), the Multidimensional Fatigue Inventory (MFI-20), and the Cognitive Failures Questionnaire (CFQ). Clinical characteristics of patients who did and did not receive RT were compared using Wilcoxon rank-sum test or Fisher's exact test. We used multivariable linear regression and reported mean score differences between comparison groups. The response rate to survey invitation was 47% (229 patients). Median age at the time of initial TSS was 55 years (18-85 years). 35% of patients were female. 25% of participants received RT a median of 2.0 years (0.1-22.5) after initial TSS, and 15% of patients had >1 additional surgery after initial TSS. The patients who received RT were younger (median age 46 v 58, p < 0.0001), had larger tumors (28 mm v 22 mm, p < 0.0001) and were more likely to have visual symptoms (65% v 34%, p = 0.0002 and were more likely to have hypopituitarism (93% v 62%, p < 0.0001). Patients completed QoL questionnaires a median of 7.7 years (1.3-29.9) after initial TSS, at which point patients with hypopituitarism reported worse energy and fatigue (SF-36 Energy/Fatigue: -7.95, p = 0.026) and cognitive function (CFQ: 5.35, p = 0.026). Patients who received RT reported significantly worse general health (SF-36 General Health Perceptions subscale: -8.44, p = 0.032), physical health (SF-36 Physical Health Composite: -4.07, p = 0.042), physical fatigue (MFI-20 Physical Fatigue subscale: 11.68, p = 0.024) and cognitive functioning (CFQ: 6.64, p = 0.0298). The largest QoL differences were seen in patients who experienced a financial stressor after treatment, independent of treatment type. These patients reported significantly worse QoL for most outcomes, including emotional well-being, physical and mental health, social functioning, energy level, and motivation. RT was associated with self-reported unstable/insecure or very dire financial circumstances (28% v 7%, p < 0.0001). Hypopituitarism, radiation therapy after TSS, and financial stressors are associated with decreased QoL in several domains, and these factors may identify patients who can benefit most from early multidisciplinary care, including financial counseling and additional psychosocial support.