Objective: The purpose of this study was to examine the effects of a 6-month therapeutic lifestyle modification (TLM) program on chemokines related to oxidative stress, inflammation, endothelial dysfunction, and arterial stiffness in subjects with metabolic syndrome (MetS). Methods: The authors performed a randomized controlled trial, assigning 52 women (mean age 62.7 ± 9.0 years) with MetS to a TLM intervention group ( n = 31) or a control group ( n = 21). The authors provided the TLM intervention group with health screening, exercise, low-calorie diet, and health education and counseling for 6 months and instructed the control group to maintain their usual lifestyle behaviors. Outcome variables included levels of myeloperoxidase (MPO), oxidized low-density lipoprotein (LDL), adiponectin, leptin, resistin, high-sensitivity C-reactive protein (hs-CRP), interleukin-1β, interleukin-6, tumor necrosis factor-alpha (TNF-α), CD40L, monocyte chemotactic protein-1 (MCP-1), retinol-binding protein 4 (RBP-4), endothelin-1, and brachial-ankle pulse wave velocity. The authors used generalized estimating equation (GEE) analyses to estimate the effects of the TLM program. Results: After the 6-month TLM program, hs-CRP levels decreased significantly, and MCP-1 levels increased at a significantly slower rate in the TLM group than they did in the control group (all p < .05). Conclusion: These results indicate that a TLM program could be effective for improving patient inflammatory states and may also be effective in preventing cardiovascular complications in subjects with MetS.