Research suggests that difficulties in emotion regulation are an important correlate of nonsuicidal self-injury (NSSI) in adults. Research examining this link in adolescents is limited by the lack of comprehensive instruments to assess difficulties in emotion regulation. Against this background, the aims of the current study were to (a) confirm the six-factor structure of the Difficulties in Emotion Regulation Scale (DERS; Gratz & Roemer, Journal of Psychopathology and Behavioral Assessment, 23(4), 253–263, 2004) in a sample of adolescent inpatients (N = 218); (b) explore the relation between different aspects of emotion dysregulation and lifetime NSSI while controlling for psychopathology and sex; and (c) assess the clinical utility of the DERS in detecting lifetime NSSI status. Fit indices obtained through Confirmatory Factor Analysis indicated that the six-factor structure of the DERS fit the data adequately and that most items loaded strongly on their respective latent factor. All six latent factors were significantly correlated with each other, with the exception of lack of emotional awareness and difficulties engaging in goal-directed behavioral when distressed. Regression analyses revealed that only the limited access to emotion regulation strategies subscale accounted for a significant portion of the variance in NSSI when controlling for other aspects of emotion dysregulation, sex, and psychopathology. Receiver Operating Characteristic analysis indicated that the DERS limited access to emotion regulation strategies subscale score has moderate diagnostic accuracy in detecting the presence of NSSI. The optimal cut-off score was 21.5 when detecting NSSI among inpatient adolescents. Results provide further support for the relation between emotion regulation difficulties and NSSI. The DERS appears to be a useful measure of detecting NSSI in clinical samples of adolescents.