Objective: One objective was to determine if cocaine-using women who did not maintain infant custody (NMC) would report more psychological distress, domestic violence, negative coping skills, lower social support and more childhood trauma than cocaine-using women who maintained custody (MC) of their infant. A second objective was to evaluate the relative contribution of psychosocial factors to infant placement. Methods: Psychosocial profiles of MC women (n = 144) were compared with NMC (n = 66) cocaine-using women. Subjects were low income, urban, African-American women who delivered an infant at a county teaching hospital. The Brief Symptom Inventory (BSI), an assessment of coping strategies (COPE), Multidimensional Scale of Perceived Social Support (MSPSS), Conflict Tactics Scale (CTS) and Childhood Trauma Questionnaire (CTQ) were administered. The associations of infant placement status to demographic factors, drug use and psychosocial measures were evaluated. Results: The NMC group reported greater overall psychological distress, psychoticism, somatization, anxiety and hostility than the MC group. The NMC group had more childhood neglect and physical abuse and used more negative coping strategies than the MC group. Lack of prenatal care [OR = 0.83, CI (0.75-0.91), p less than 0.0001], heavier prenatal cocaine use [OR = 2.55, CI (1.13-4.34), p less than 0.007], greater psychological distress [OR = 2.21, CI (1.13-4.34), p less than 0.02] and a childhood history of emotional neglect [OR = 1.10, CI (1.02-1.19), p less than 0.02] were associated with increased likelihood of loss of infant custody after control for other substance use and demographic variables. Conclusions: NMC women have more negative psychological and behavioral functioning post-partum than MC women. Less prenatal care and greater cocaine use, psychological distress and maternal childhood emotional neglect are associated with the post-partum placement of infants born to cocaine-using women. Practice implications: Results of this study indicate that poor, urban women who use cocaine prenatally display several measurable differences on psychosocial and behavioral risk factors based on child placement status. Among these risk factors heavier cocaine use, lack of prenatal care, more severe psychological symptoms and early childhood experiences of emotional neglect increase the likelihood of loss of infant custody. Routine, objective assessments of psychosocial and behavioral characteristics of women who use cocaine during pregnancy can aid Child Protective Service workers and clinicians by providing baseline data from which to tailor interventions and set improvement criteria for mother-child reunification.