Background: The assessment of health related quality of life (HRQOL) has increasingly been recognized as an important adjunct to medical outcome parameters in the monitoring of cystic fibrosis (CF) patients and in clinical studies. The Cystic Fibrosis Questionnaire (CFQ) is a disease-specific HRQOL instrument for CF patients developed in France. Translations are currently being validated in four different countries. The aim of the present study was to validate the German adaptation of the CFQ-14+. Method: On the basis of results from a first dataset (n = 197 CF adolescent and adult patients), revisions were made and retested in a second sample of 103 patients. Results: The final revised version showed good construct validity. The same nine HRQOL domains as in the French original CFQ-14+ emerged from the analyses as structurally robust scales. The internal consistencies of the HRQOL scales ranged from 0.71 to 0.94. The instrument''s clinical validity was supported by severely ill patients reporting lower HRQOL than less severely ill patients on most scales. Conclusion: We conclude that the evidence supports the validity and reliability of the instrument. An important future area of application is the use in comparative multi-center international studies.