This was an observational and economic survey performed in primary care practices throughout Spain to assess the effectiveness and direct medical costs derived from antibiotic treatment of exacerbations of chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD) in primary care. A total of 252 physicians included 1456 valid patients, 80% were male and the mean age was 68.2 years (SD = 9.8). The antibiotic treatment administered was moxifloxacin in 575 (39.5%), amoxicillin/clavulanate in 460 (31.6%) and clarithromycin in 421 (28.9%). No significant differences were found in clinical and demographic characteristics between treatment arms. The 30-days follow-up visit was completed by 1097 (75%) patients, who were therefore valid for economic evaluation. During follow-up, 440 new medical visits were generated, 69 patients required attendance in emergency wards (6.3%) and 22 were hospitalised (2%). The overall mean cost of exacerbation was Euro 118.58 [95% confidence interval (CI) = Euro 92.2-144.9] and Euro 52.44 (44.2%) were due to therapeutical failure. The mean cost of exacerbation was Euro 111.46 (95% CI = Euro 73.4-149.5) for patients treated with moxifloxacin, Euro 109.45 (95% CI = Euro 68.2-150.7) for those treated with amoxicillin/clavulanic acid and Euro 138.95 (95% CI = Euro 89.4-188.5) for patients receiving clarithromycin. In conclusion, a significant number of patients require new medical interventions after ambulatory treatment of exacerbations of CB or COPD. The mean cost of an exacerbation was Euro 118.58 and failure was responsible for 44.2% of the total cost of exacerbation.