© 2017 Background: The Cystic Fibrosis Questionnaire-Revised (CFQ-R + 14) is a disease-specific, health-related quality of life instrument for cystic fibrosis (CF) patients ≥ 14 years. We have developed a Spanish electronic version of the CFQ-R (e-CFQ-R + 14 Spain). Our aim was to compare the paper and electronic versions and to validate the electronic version. Methods: Fifty CF patients completed the study. All answered the paper and electronic versions on day 1 and repeated the e-CFQR version 15 days later. Results: Concordance between the electronic and paper copy versions was high, with correlations above 0.9 in all domains. Test-retest reliability of the e-CFQ-R results was strong, with coefficients ranging from 0.8 to 0.9. Conclusions: The e-CFQ-R version is reliable and valid and can replace the paper copy, thus simplifying the assessment of quality of life. It also provides immediate results with no errors in scoring. It is a useful new tool in CF care.