BACKGROUND: Several studies demonstrated an association of homocysteine plasma levels and the plasma lipoprotein profile. This cross-sectional pilot study aimed at analyzing whether blood levels of the two important cofactors of homocysteine metabolism, folate and vitamin B12, coincide with the lipoprotein profile. METHODS: In a retrospective single center approach, we analyzed the laboratory database (2003-2006) of the University Hospital Bonn, Germany, including 1743 individuals, in whom vitamin B12, folate and at least one lipoprotein parameter had been determined by linear multilogistic regression. RESULTS: Higher folate serum levels were associated with lower serum levels of low density lipoprotein cholesterol (LDL-C; Beta = -0.164; p < 0.001), higher levels of high density lipoprotein cholesterol (HDL-C; Beta = 0.094; p = 0.021 for trend) and a lower LDL-C-C/HDL-C-ratio (Beta = -0.210; p < 0.001). Using ANOVA, we additionally compared the individuals of the highest with those of the lowest quartile of folate. Individuals of the highest folate quartile had higher levels of HDL-C (1.42 +/- 0.44 mmol/l vs. 1.26 +/- 0.47 mmol/l; p = 0.005), lower levels of LDL-C (3.21 +/- 1.04 mmol/l vs. 3.67 +/- 1.10 mmol/l; p = 0.001) and a lower LDL-C/HDL-C- ratio (2.47 +/- 1.18 vs. 3.77 +/- 5.29; p = 0.002). Vitamin B12 was not associated with the lipoprotein profile. CONCLUSION: In our study sample, high folate levels were associated with a favorable lipoprotein profile. A reconfirmation of these results in a different study population with a well defined status of health, diet and medication is warranted.