Little is known about the cardiovascular effects of modest weight loss. To determine whether weight losses limited to 5–10 % are sufficient to produce cardiovascular health benefits, data from 401 overweight and obese adults who enrolled in a behavioral weight loss program from 2003 to 2011 were analyzed. Primary outcomes were changes in fasting glucose, triglycerides, and cholesterol. Patients who lost 5–10 % showed significant reductions in triglycerides, total cholesterol, and low-density lipoprotein (LDL) cholesterol. Patients who lost >10 % experienced significantly greater improvements in triglycerides, total cholesterol, and LDL cholesterol than patients losing less. For higher-risk patients, those who lost 5–10 % significantly reduced fasting glucose, triglycerides, and total cholesterol; those who lost >10 % improved on all risk factors (except HDL cholesterol) and to a significantly greater degree than those losing less. Five to 10 % weight losses produced improvements in cardiovascular risk factors, but greater weight losses were associated with even greater improvement.