To investigate symptom profiles and clinical signs in subjects with dry eye and normal subjects in a cross-sectional multicenter study. Subjects aged 35 to 65 were recruited according to dry eye diagnostic codes and telephone interview and completed the Dry Eye Questionnaire 2001, among others, and underwent dry eye clinical tests. Subjects (122) included 28 control subjects (C), 73 with non-Sjögren's keratoconjunctivitis sicca (non-SS KCS) and 21 with Sjögren's syndrome (SS). Subjects with SS or non-SS KCS reported discomfort and dryness most frequently and that many symptoms worsened over the day and were quite bothersome. Groups were significantly different in corneal fluorescein staining, conjunctival lissamine green staining, Schirmer 1 tear test, and tear break-up time (TBUT; chi2 and Kruskal-Wallis, P<0.0001). Statistically significant, but moderate, correlations were found between the frequency and evening intensity of dryness and discomfort and TBUT, Schirmer's tear test, overall corneal fluorescein staining, and temporal lissamine green conjunctival staining (Spearman r=0.31-0.45, P<0.01). Symptoms were moderately to highly correlated with the clinician's global grading of severity and highly correlated to patient's self-assessment of severity (r=0.46-0.86, P<0.0001), whereas signs showed lower correlations (r=0.22-0.46, P<0.0001). Subjects with SS or non-SS KCS reported frequent and intense ocular surface symptoms in the evening, some of which correlated moderately with clinical test results. The global clinician grade of dry eye correlated more highly with patient symptoms than did clinical signs, suggesting that patient symptoms influence dry eye diagnosis and grading of dry eye more than clinical test results.