This seminal study systematically investigated the impact of PWS on healthy siblings’ psychosocial, emotional and behavioral adjustment and health related quality of life (HRQOL). It also evaluated healthy siblings’ perceptions of caregiving availability and the impact this had on their psychosocial adjustment. Caregiving was defined in a relational context associated with psychosocial adjustment that included social, emotional and behavioral dimensions. Quantitative and qualitative data was gathered from measures administered to 12 mothers and 13 healthy siblings in families with a child diagnosed with PWS. Four major findings were revealed: (1) moderate to severe levels of traumatic stress reaction were reported by 12 healthy siblings in the sample, one healthy sibling reported mild symptoms of traumatic stress reaction; (2) healthy siblings’ traumatic stress reaction symptoms were strongly associated with experiences of unresolved attachment; (3) healthy siblings’ perceived loss of caregiving availability and unresolved attachment were significantly related to their psychosocial adjustment; and, (4) healthy siblings’ unresolved quality of attachment and psychosocial-emotional and behavioral functioning were significantly correlated with mothers’ self-reported levels of stress. Some positive outcomes were also found. Suggestions are made for developing appropriate evaluative, therapeutic and support services to ensure that the needs of parents and healthy siblings in families with a child diagnosed with PWS are met.