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Abstract Background Integrated disease management with self-management for Chronic Obstructive Pulmonary Disease (COPD) is effective to improve clinical outcomes. eHealth can improve patients’ involvement to be able to accept and maintain a healthier lifestyle. Eventhough there is mixed evidence of the impact of eHealth on quality of life (QoL) in different settings. Aim The primary aim of the e-Vita-COPD-study was to investigate the effect of use of eHealth patient platforms on disease specific QoL of COPD patients. Methods We evaluated the impact of an eHealth platform on disease specific QoL measured with the clinical COPD questionnaire (CCQ), including subscales of symptoms, functional state and mental state. Interrupted time series (ITS) design was used to collect CCQ data at multiple time points. Multilevel linear regression modelling was used to compare trends in CCQ before and after the intervention. Results Of 742 invited COPD patients, 244 signed informed consent. For the analyses, we only included patients who actually used the eHealth platform (n = 123). The decrease of CCQ-symptoms was 0.20% before the intervention and 0.27% after the intervention; this difference in slopes was statistically significant (P = 0.027). The decrease of CCQ-mental was 0.97% before the intervention and after the intervention there was an increase of 0.017%; this difference was statistically significant (P = 0.01). No significant difference was found in the slopes of CCQ (P = 0.12) and CCQ-function (P = 0.11) before and after the intervention. Conclusion The e-Vita eHealth platform had a potential beneficial impact on the CCQ-symptoms of COPD patients, but not on functional state. The CCQ-mental state remained stable after the intervention, but this was a deterioration compared to the improving situation before the start of the eHealth platform. Therefore, health care providers should be aware that, although symptoms improve, there might be a slight increase in anxiety and depression after introducing an eHealth intervention to support self-management. Trial registration Our study is registered in the Dutch Trial Register (national registration of clinical trails, mandatory for publication) with number NTR4098 and can be found at http://www.trialregister.nl/trial/3936. Date registered: 2013-07-31. First participant: 2014-01-01.