STUDY DESIGN: Cross-sectional study. OBJECTIVES: To compare pressure pain thresholds (PPTs) between adolescent females diagnosed with patellofemoral pain syndrome (PFPS) and gender- and age-matched controls without musculoskeletal pain. BACKGROUND: PFPS is prevalent among adolescents and may be associated with reduced PPT both locally and remotely from the site of reported pain. This may indicate altered central processing of nociceptive information. However, this has never been investigated in adolescents with PFPS. METHODS: Adolescents with PFPS and a comparison group without musculoskeletal pain were recruited from a population-based cohort of students from 4 upper secondary schools, aged 15 to 19 years. All 2846 students within that age range were invited to answer an online questionnaire regarding musculoskeletal pain. The students who reported knee pain were contacted by telephone and offered a clinical examination by an experienced rheumatologist, who made a diagnosis. PPTs were measured at 4 sites around the knee and 1 site on the tibialis anterior in the 57 female adolescents diagnosed with PFPS and in 22 female adolescents without musculoskeletal pain. RESULTS: Adolescents with PFPS, compared to controls, had significantly lower PPTs (26%-37% [100-178 kPa]) at each of the 4 sites around the knee, suggesting localized hyperalgesia. On the tibialis anterior, adolescents with PFPS had a 33% (159 kPa) lower PPT (distal hyperalgesia) compared with controls. CONCLUSION: These findings suggest that adolescent females with PFPS have localized and distal hyperalgesia. These findings may have implications for treating PFPS, as both peripheral and central mechanisms may be driving the pain. Registered at clinicaltrials.gov (NCT01438762).