© 2019, American Cleft Palate-Craniofacial Association. Objectives: Despite the potential psychological impact of a diagnosis of cleft lip and/or palate (CL/P) on parents, few large-scale studies currently exist. Utilizing data extracted from The Cleft Collective Birth Cohort Study, the current study aimed to examine the psychological impact of the diagnosis on parent and family functioning and to identify risk and/or protective factors contributing to parental adjustment in order to inform future psychological intervention. Methods: Parent-reported questionnaire data were extracted for 1163 parents (644 mothers and 519 fathers). Outcome measures included the PedsQL-Family Impact Module, the Perceived Stress Scale, the Hospital Anxiety and Depression Scale, and a condition-specific tool designed by the Psychology Clinical Excellence Network. Results: Overall, findings suggest that parents adjust well to the diagnosis. Factors found to be protective against psychological distress for both mothers and fathers included a positive life orientation, satisfaction with health care, and relationship satisfaction. Close friendships were also protective against depression in mothers. Risk factors for mothers included the presence of a prior mental health condition, and stressful life events during pregnancy. Risk factors for fathers included being older at the time of conception, and recently being absent from work. Conclusions: Findings suggest a need for appropriate psychological screening of both parents following a diagnosis of CL/P and emphasize the importance of coordinated multidisciplinary care for psychological health. Preventative models of intervention to strengthen familial relationships and build resilience require further investigation.