Alternate day fasting (ADF) with a low-fat (LF) diet increases low-density lipoprotein (LDL) particle size. Whether these beneficial effects can be reproduced by a high-fat (HF) ADF diet is unclear. This study compared an ADF-HF to an ADF-LF diet on plasma lipids, LDL size and high-density lipoprotein (HDL) size. Thirty-five obese subjects were randomized to an ADF-HF or ADF-LF diet for 10 weeks. Body weight decreased (P<0.0001) by 4.3±1.0 kg (4.8±1.1%) and 3.7±0.7 kg (4.2±0.8%) in the ADF-HF and ADF-LF group, respectively. LDL cholesterol was reduced (P<0.0001) by 19±8 mg/dl (18±5%) by ADF-HF and 28±7 mg/dl (25±3%) by ADF-LF. LDL particle size increased (P<0.005) by 3±1 Å in both groups. The proportion of small LDL particles decreased (P<0.005) by 8±2% and 11±3% in the ADF-HF and ADF-LF groups, respectively. HDL cholesterol and HDL size remained unchanged. Thus, our results suggest that the ADF-HF diet is equally as effective as the ADF-LF diet in improving LDL particle size and distribution.