OBJECTIVES: To evaluate the cost of  biweekly oxaliplatin plus oral capecitabine (OXXEL) versus oxaliplatin combined with leucovorin-modulated 5-Fluorouracil (5-FU) given as i.v. bolus every 2 weeks (OXAFAFU) in patients with metastatic colorectal cancer (MCRC) in Italy. METHODS: We conducted a multicenter, retrospective longitudinal treatment-cost analysis. Direct medical cost attributable to MCRC were quantified using 2008 prices and tariffs. The analysis was applied to a time horizon of 6 months. The study was conducted from the perspective of the National Healthcare Service (NHS). RESULTS: A total of 322 patients (59.9% males; mean age 65,2 ± 9.4 yrs) were analysed. Mean total cost per patient over follow-up period was estimated at €5242.18 ± 2542.06 and €6732.80 ± 3423.72 in the Capecitabine and 5-FU arms respectively  (P<0.0001). CONCLUSIONS: The study estimated that oral capecitabine administration would produce a saving of €1490.62 to the NHS. The differences in cost between the two arms is determined by the administration route (i.v. vs. oral administration). Therefore the important economic and practical advantage of capecitabine oral home-based therapy is the reduced number of hospital visit and the relative costs. Avoiding the hospital access fees reduces the impact of higher acquisition cost of capecitabine. Moreover capecitabine in comparison to the 5-FU regimen  was associated with lower complication.  Therefore oral capecitabine may represent a valid alternative in the management of metastatic colorectal cancer.