BACKGROUND Patients with Raynaud's phenomenon (RP) have vasomotor dysregulation, mainly cause by dysfunction of the endothelium. Since homocysteine has been found to be damaging to endothelial cells, we investigated the concentrations of plasma homocysteine, folate and vitamin B12 in patients with primary or secondary RP compared to healthy individuals. PATIENTS AND METHODS We measured the concentrations of plasma fasting homocysteine, folate and vitamin B12 in a group of healthy individuals (n = 45) and in patients with primary (n = 26) or secondary RP (n = 42). RESULTS Median homocysteine levels in healthy controls and in patients with primary RP, secondary RP were 7.9 (IQR 4.1 to 11.8) 9.8 (IQR 5.1 to 14.4), and 10.6 (6.0 to 15.3) mumol/L, respectively. Patients with primary and secondary RP had significantly higher homocysteine concentration compared to healthy controls (Kruskal Wallis p = 0.01). After matching for age and sex, patients with either primary or secondary RP showed significantly higher homocysteine levels (Wilcoxon p < 0.0001). No significant differences between the three groups were found concerning serum levels of vitamin B12 (p = 0.9) and serum folate levels (p = 0.2). CONCLUSION These data demonstrate that patients with RP have higher plasma levels of homocysteine. No significant differences in folate and vitamin B12 levels were found between patients with primary RP, secondary RP, and healthy individuals. These data suggest that homocysteine may play a role in RP and may provide new clues in understanding of the vasomotor dysregulation.