The objective of the present study was to examine several dimensions of quality of life (QoL) and fatigue in patients with adrenal incidentaloma. This was a case-control study designed to analyze patient outcomes using three validated generic QoL questionnaires, EQ-5D, SF-36, and MFI-20, the results of which were compared to those obtained for age- and sex-matched controls. The study population comprised 139 consecutive patients with nonfunctioning adrenal masses (104 females, 35 males; age 59.1 ± 10.8) and 139 age- and sex-matched controls. Reduced QoL was found in patients with adrenal incidentaloma as compared to controls. Dimensions of QoL that were notably affected included mobility (P = 0.03), performance of usual activities (P = 0.002), and anxiety/depression (P = 0.04) as evaluated using the EQ-5D; physical functioning (P < 0.001), physical role (P < 0.001), general health (P < 0.001), vitality (P = 0.001), social functioning (P = 0.001), and emotional role (P < 0.001) as evaluated using the SF-36; and physical fatigue (P = 0.04) as assessed using the MFI-20 questionnaire. In addition, perceived health on a visual analogue scale was also significantly lower in patients than in controls (64.8 ± 19.2 vs. 77.1 ± 15.1; P < 0.001). Patients with adrenal incidentaloma reported reduced QoL and a higher level of physical fatigue compared to age- and sex-matched controls. This subject will benefit from further studies comparing QoL outcomes of laparoscopic adrenalectomy versus no treatment in patients with adrenal incidentaloma.