Background Capecitabine and oxaliplatin are both synergistically active against metastatic colorectal cancer (MCRC). We evaluated our experience at two centers with capecitabine and oxaliplatin combination (XELOX) in previously untreated patients with MCRC. Patients and methods We reviewed medical records of 85 previously untreated patients with MCRC who received first-line XELOX regimen. Oxaliplatin was given at a dose of 130 mg/m(2) on day I in combination with capecitabine 1500 mg/m(2) /day on days 1-14 every 3 weeks. Results Seventy six of 85 patients were evaluated for response and toxicity. Patients with a follow up of less than 6 months were excluded from the study. Objective response rate was 46% including 8 complete responses (10.5%) and 27 partial responses (35.5%). Additionally, 20 patients (26.3%) had disease stabilization at least 3 months after the treatment. The patients were followed for a median 12.5 months (range 2-32). Median time to disease progression (TTP) was 11 months (range 2-27 months). Median overall survival (OS) time has not yet been reached. One-year survival rate was 66%. Toxicity was modest with infrequent grade 3-4 adverse effects. Conclusion XELOX is an active regimen against MCRC in the first-line setting with favorable toxicity profile. Our results appear to be comparable, if not superior, to the results of other reports of first-line XELOX therapy in respect to objective response rates, survival data, and safety profile. Convenience with oral administration of every 3-week schedule makes XELOX regimen a compelling therapeutic option in the treatment of first-line MCRC.