The diagnosis of chronic cough involves a thorough clinical assessment to rule out the presence of common causes such as asthma, reflux, and rhino-sinus syndromes. Data of 1300 (933 females) chronic coughers referred to the Florence Cough Clinic were retrospectively evaluated on four visits (V1-V4) to identify factors associated with treatment failure. Participants rated the cough disturbance by means of a 0?9 cough score (CS). An association between cough and its commonest causes was established and treatments administered accordingly. Patients with a CS>1 at V4 were defined as ?non-responders? to treatments, and a logistic regression model was used to identify factors associated with treatment failure. At V1 most patients reported one or more symptoms suggestive of the most common causes of chronic cough while 6% reported exclusively cough. At visit 2 CS decreased from 5.25±0.13 to 1.30±0.14, (p<0.01) in about 60% of the population, and 45% of them had cough resolution at V4 about. In non-responder patients, CS values recorded at visit 1 did not significantly change throughout the follow-up. Cough duration (OR: 1.09, 95% CI 1.02-1.12) and CS at V1 (OR: 1.12, 95% CI 1.06-1.22) were factors predictive (P<0.01) of treatment failure, whereas male gender (OR: 0.62, 95% CI 0.40-0.96) and coughing during night (OR: 1.65, 95% CI 1.1762.32) were significantly (P<0.01) associated with cough resolution. Symptom-driven treatments determines the resolution in less than half of the study population. The remaining patients, identified early by higher CS values and longer cough duration, could be defined as suffering from "refractory/unexplained" chronic cough.