Little is known about which risk factors longitudinally predict non-suicidal self-injury (NSSI) during adolescence, a period when these self-injurious behaviors become alarmingly prevalent. We prospectively studied the rates, course, and longitudinal prediction of NSSI from early through middle adolescence with a community sample of 103 youth (ages 11-14) who were assessed for NSSI at baseline and 2 _ years later (94% retention; final N=97). Multiple risk factors (temperament, cognitive and interpersonal vulnerabilities, stressors; youths’ and mothers’ depression) were examined as prospective predictors of NSSI over the 2_ year follow-up. Analyses showed that 18% of youth engaged in NSSI over the 2_-year follow-up; 14% for the first time. Distal risks (assessed at baseline) that differentiated youth who engaged in NSSI from those who did not included negative cognitive style and mothers’ prior depression. Proximal factors (assessed 2 years after baseline) that differentiated NSSI from non-NSSI youth included stressors, depressive symptoms, poor relationship quality, excessive reassurance seeking, and mothers’ onset of depression. Several of these factors predicted new engagement of NSSI over 2_ years.