Objective Examine longitudinal relationships between spiritual coping and psychological adjustment among adolescents with chronic illness. MethodsAdolescents (N = 128; M = 14.7 years) with cystic fibrosis or diabetes completed measures of spiritual coping and adjustment at 2 time points ∼2 years apart; parents also reported on adolescent adjustment. Prospective relationships between spiritual coping and adjustment were evaluated with an autoregressive cross-lagged path model. ResultsPositive spiritual coping predicted fewer symptoms of depression and less negative spiritual coping over time, whereas negative spiritual coping predicted more positive spiritual coping. Depressive symptoms predicted higher levels of negative spiritual coping and conduct problems over time. The results did not vary by disease. Conclusions Positive spiritual coping may buffer adolescent patients from developing depression and maladaptive coping strategies. Results also highlight the harmful role of depression in subsequent behavior difficulties and maladaptive coping. Addressing spiritual beliefs and depressive symptoms in pediatric medical care is warranted. © 2014 The Author.