Objective: To examine the association between sexual activity among urban adolescent girls and four global measures of psychosocial adaptation (academic motivation, school achievement, depressive symptoms, and expectations about the future). Method: Data derived from the Social and Health Assessment, a self-report survey administered in 1998 to students in the public school system in New Haven, CT (149 classes at 17 middle and high schools). Results: Of 1,413 respondents (57% black, 28% Hispanic; mean age 13.4 [+ or -] 1.7 years), 414 (29%) acknowledged prior sexual intercourse; the proportions of sexually active girls in 6th, 8th, and 10th grades were 14%, 30%, and 50%, respectively. In multivariate analyses of covariance, sexual activity was significantly associated with all four measures of psychosocial adaptation (p < .001). Other correlates of at least one measure of maladaptation included socioeconomic status, sensation seeking, and lower school grade (p < .001 for each), peer pressure (p < .01), and black ethnicity, and the interaction of sexual activity by lower school grade (p < .05 for each). Conclusions: Compared with their sexually naive peers, sexually active adolescent girls had lower scores on global measures of psychosocial adaptation. These findings have clinical, policy, and research relevance to a vulnerable population at high risk of teenage pregnancy and sexually transmitted diseases. J. Am. Acad. Child Adolesc. Psychiatry, 2005;44(4):358-367. Key Words: sexual activity, pregnancy, sexually transmitted diseases, human immunodeficiency virus, psychosocial adaptation