OBJECTIVES: To estimate the healthcare direct costs of an episode of extensive superficial or deep uncomplicated foot ulcer of neuropathic origin in patients with diabetes in Spain and identify the key factors that influence total costs. METHODS: A retrospective observational study of patients with an episode of foot ulcer during the period from January 2007 through December 2008 in 10 Spanish centres was performed. Data about sociodemographic characteristics, duration of the episode and healthcare-related resources were considered. The following resources were collected from hospital records: inpatient hospitalisations, surgeries, outpatient visits (specialists and primary care physician), diagnostic procedures, laboratory tests, ulcer-related cures, antibiotics and orthotic devices. Unitary cost (€, year 2009 values) data were taken from a Spanish Database of Health Costs and the Catalogue of Medicinal Products. RESULTS: Ninety-two patients (29.3% with one or more previous ulcers) with a foot ulcer episode were identified. The majority of cases were males (76.9%). Patients’ mean age was 65.20±10.90 years and 50.0% of these were retired. Average duration of an ulcer episode was 131±123 days. Most prevalent comorbidities were arterial hypertension (62.0% of cases), diabetic retinopathy (41.3%), renal impairment (30.4%), dyslipidemias (25.0%) and myocardial infarction (19.6%). Concomitant infections during the episode were reported in 33.7% of patients. The average cost per patient and ulcer episode was €17,262 (95% confidence interval [CI], €11,315, €23,715). The most important categories of costs were for surgeries (€7054, 95%CI, €6043-€8200, 40.9% of costs), inpatient hospitalisations (€6197, 95%CI, €3605-€8878, 35.9% of total costs), and ulcer-related cures (€2864, 95%CI, €1127-€4759, 16.6% of total costs). Among surgeries, the most relevant were debridements and amputations. CONCLUSIONS: An episode of a neuropathic extensive superficial or deep uncomplicated diabetic foot ulcer generates a substantial economic burden, with a mean cost per patient of €17,262. Surgeries, hospitalisations and ulcer-related cures represent 93.4% of total costs.