We investigated the association between retinol-binding protein 4 (RBP4) and apolipoprotein B (ApoB)-containing lipoproteins. Obese or overweight, hypertriglyceridemic patients underwent the following interventions for 3 months: (1) Diet (n = 20), (2) Diet + fenofibrate (n = 18), (3) Diet + rimonabant (n = 8). Circulating RBP4 decreased during dietary treatment. The percentage change in RBP4 was positively correlated with the percentage changes in very-low density lipoprotein cholesterol (r = .570, P = .02), low-density lipoprotein cholesterol ([LDL-C]; r = .605, P = .01), ApoB (r = .705, P = .007), and small dense LDL-C ([sdLDL-C]; r = .872, P < .001). The percentage change in RBP4 was the best predictor of the percentage changes in sdLDL-C and ApoB. Rimonabant treatment reduced RBP4, whereas fenofibrate increased RBP4 during the first month of therapy followed by a subsequent decrease. In conclusion, RBP4 may significantly influence the metabolic pathways responsible for changes in ApoB lipoprotein subspecies, thus RBP4 may be associated with cardiovascular disease risk.