While quick diagnosis units (QDUs) have expanded as an innovative cost-effective alternative to admission for workup, studies investigating how QDUs compare are lacking. This study aimed to comparatively describe the diagnostic performance of the QDU of an urban district hospital and the QDU of its reference general hospital.This was an observational descriptive study of 336 consecutive outpatients aged ≥18 years referred to the QDU of a urban district hospital in Barcelona (QDU1) during 2009 to 2016 for evaluation of suspected severe conditions whose physical performance allowed them to travel from home to hospital and back for visits and examinations. For comparison purposes, 530 randomly selected outpatients aged ≥18 years referred to the QDU of the reference tertiary hospital (QDU2), also in Barcelona, were included. Clinical and QDU variables were analyzed and compared.Mean age and sex were similar (61.97 (19.93) years and 55% of females in QDU1 vs 60.0 (18.81) years and 52% of females in QDU2; P values = .14 and .10, respectively). Primary care was the main referral source in QDU1 (69%) and the emergency department in QDU2 (59%). Predominant referral reasons in QDU1 and 2 were unintentional weight loss (UWL) (21 and 16%), anemia (14 and 21%), adenopathies and/or palpable masses (10 and 11%), and gastrointestinal symptoms (10 and 19%). Time-to-diagnosis was longer in QDU1 than 2 (12 [1-28] vs 8 [4-14] days; P < .001). Malignancy was more common in QDU2 than 1 (19 vs 13%; P = .001). Patients from both groups with malignancy, aged ≥65 years and requiring >2 visits to be diagnosed were in general more likely to be males, to have UWL and adenopathies and/or palpable masses but less likely anemia, to undergo more examinations except endoscopy, and to be referred onward to specialist outpatient clinics.Despite some differences, results showed that, for diagnostic purposes, the overall performance and effectiveness of QDUs of urban district and reference general hospitals in evaluating patients with potentially serious conditions were similar. This study, the first to compare the performance of 2 hospital-based QDUs, adds evidence to the opportunity of producing standardized guidelines to optimize QDUs infrastructure, functioning, and efficiency.