© Copyright 2019, Mary Ann Liebert, Inc., publishers 2019. It is well known that total and intentional weight loss (IWL) are associated with reductions in cardiovascular disease (CVD) risk factors, however, associations with unintentional weight loss (UWL) have not been studied. Methods: We examined annual changes in blood pressure and lipids associated with UWL versus IWL in 576 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study who had lost weight over one of two time intervals (i.e., study years 5-7 or 7-10) and reported whether the weight loss was intentional at the end of the interval. Results: After adjusting for age, sex, race, and field center, an annual weight loss smaller than 6% resulted in small improvements in lipids that were similar regardless of intentionality. When annual weight loss was ≥6%, UWL was associated with less reduction in total cholesterol (-0.2 vs. -10.4 mg/dL), low-density lipoprotein cholesterol (-3.2 vs. -9.4 mg/dL), and triglycerides (-0.5 vs. -19.0 mg/dL) compared with IWL. Intentionality was not associated with the size of changes in blood pressure (systolic blood pressure: -2.7 vs. -2.0 mmHg; diastolic blood pressure: -2.2 vs. -1.3 mmHg) and high-density lipoprotein cholesterol (3.2 vs. 2.7 mg/dL). Conclusions: Substantial UWL may be accompanied or preceded by other biological changes in this young adult population that alter changes in CVD risk factors that are associated with IWL.