Background:The concept of clinical control has been proposed as an instrument for evaluating patients with COPD. However, the possible association between clinical control,reduced symptom severity and HRQoL has yet to be confirmed.Method: This multicentre, prospective and observational study was carried out in pulmonology clinics in Spain. The patients were followed up for six months, with a baseline visit (V0), followed by visits at three months (V1) and six months (V2). Clinical control was determinedat V1, with the application of both clinical criteria and the COPD assessment test (CAT). All patients reported their symptoms by a validated symptom diary (E-RS) using a portable device, and their HRQoL was assessed using the EQ5D questionnaire. The relationship between clinical control and E-RS andHRQoL during follow-up was assessed.Results: A total of126 patients were screened. After application of the inclusion/exclusion criteria, 93 were finally included (mean age 66 ± 8 years, 84.9% male), with a mean FEV1predicted of 49.8% ± 16.5%. Of these patients, 44 (47.3%) achieved clinical control at V1, according to CAT criteria, and 50 (53.8%), according to clinical criteria. The E-RS scores differed between controlled and uncontrolled patients at all time points, both according to CAT (mean differences of -4.6, -5.6 and -6.2 units at V0, V1 and V2 respectively, p<0.005 for all comparisons) and to clinical criteria (mean differences of -3.3, -5-6 and -4.99 units, respectively, p<0.005 for all comparisons). The controlled patients also presented a significantly better HRQoL, measured by the EQ5D questionnaire(mean difference 0.13and 0.10 at V2 by CAT or clinical criteria, respectively, p<0.05).Conclusions:Clinical control in patients with COPD, whether measured by CAT or by clinical criteria, is associated with a lower symptom load and a better HRQoL.