OBJECTIVE: Adolescents with cystic fibrosis (CF) often face a unique set of difficulties and challenges as they transition to adulthood and autonomy while also managing a progressive illness with a heavy treatment burden. Coping styles have been related to changes in physical health among youth with chronic illness more generally, but the directionality of these links has not been fully elucidated. Therefore, the objective of this study was to evaluate bidirectional links between coping styles and physical health indicators among adolescents with CF over time. METHODS: Adolescents (N = 79, 54% female) recruited from inpatient and outpatient CF clinics at two sites completed questionnaires assessing secular and religious/spiritual coping styles at two time points (18 months apart, on average). Health indicators including pulmonary functioning, nutritional status, and days hospitalized were obtained from medical records. RESULTS: More frequent hospitalizations predicted lower levels of adaptive secular coping over time. However, poorer pulmonary functioning predicted higher levels of positive religious/spiritual coping. The number of days hospitalized was related to adaptive secular coping and negative religious/spiritual coping. CONCLUSIONS: Among youth with CF, physical health functioning is more consistent in predicting coping strategies than the reverse. Poorer pulmonary functioning appears to enhance adaptive coping over time, suggesting resilience of adolescents with CF, while more frequent hospitalizations may inhibit the use of adaptive coping strategies. Findings support the use of interventions aimed at promoting healthy coping among hospitalized adolescents with CF.