AIM: To evaluate the signs and symptoms of dry eye disease (DED) in adolescents. METHODS: This was a cross-sectional, case-control study and outpatients aged 10 to 19y were recruited from six eye clinics of various practices and locations in Japan, and 253 non-DED subjects and 70 DED patients were enrolled. Participants were examined for DED-related signs. Patients were also interviewed to ascertain the presence or absence of six common DED-related symptoms: dryness, irritation, pain, eye fatigue, blurring, and photophobia. Main outcome measures were differences in signs and symptoms of dry eye disease between boys and girls. RESULTS: Of the 323 adolescents recruited, 70 (21.7%) were diagnosed with DED. Significant differences between the non-DED and DED groups were found for short tear break-up time (BUT; ≤5s; P=0.000) and superficial punctate keratopathy (SPK; staining score ≥3; P=0.000). Late adolescent girls reported fewer symptoms than late adolescent boys, although their DED-related signs were worse compared to other groups. The prevalence and severity of DED were similar in the Tokyo area compared with suburban and local areas but myopic errors were worse. CONCLUSION: We find that adolescents reported symptoms of DED similar to those found in adults, and the majority have short BUT-type DED. The prevalence and severity of DED in late adolescent girls is comparable with adults. Adolescents with DED are underserved and we believe that DED is a hidden but potentially serious health problem for this age group.