Background: Positive spiritual coping in adolescent patients with cystic fibrosis (CF) is associated with better emotional functioning, but its role in health outcomes is unknown. Methods: Adolescents diagnosed with CF (n = 46; M = 14.7 years) reported on their use of positive and negative spiritual coping. Measures of nutrition status (BMIp), pulmonary function (%FEV1), and hospitalizations were obtained for a five-year follow up period. Changes in BMIp and %FEV1 scores were estimated with hierarchical linear models; days hospitalized were modeled with negative binomial regression. Results: Positive spiritual coping was associated with slower decline in pulmonary function, stable vs. declining nutritional status, and fewer days hospitalized over the five-year period. Negative spiritual coping was associated with higher BMI percentile at baseline, but not with health outcomes over time. Conclusions: These results suggest that positive spiritual coping plays a key role in maintaining long-term health of adolescent patients with CF. © 2014 European Cystic Fibrosis Society.