In old age, both apathy and depression have been associated with an increased cardiovascular disease (CVD) risk. This study evaluated the mediating role of cardiovascular risk factors in the relationship of apathy and mood symptoms with incident CVD. Methods: Prospective cohort study of 1,790 community-dwelling older individuals (70-78 years) without a history of CVD or stroke. At baseline, apathy and mood symptoms were assessed with the 15-item Geriatric Depression Scale (GDS-15), of which three items represent apathy symptoms. The mediational risk factors included were diabetes mellitus (DM), body mass index (BMI), current smoking, physical inactivity, systolic blood pressure, and total cholesterol. Incident CVD was evaluated after two years of follow-up. Data were analyzed using structural equation modeling (SEM). Results: Incident CVD occurred in 59 (3.3%) participants. Apathy symptoms had a significant estimated total effect on incident CVD, with increases of 2.2% for each unit increase in apathy score. Of this total effect, 22.7% was due to the mediational effects of physical inactivity (13.6%), current smoking (4.5%), and DM (4.5%). The remaining 77.3% was due to direct effects reflecting other mediational dynamics. No significant (in)direct effects of mood symptoms on incident CVD were found. Conclusions: Physical inactivity, smoking, and DM account for nearly one-fourth of the variation reflecting the link between apathy symptoms and incident CVD. This illustrates the relevance of unfavorable health behaviors and assessment of DM in older individuals with apathy. The majority of the effect of apathy symptoms on incident CVD is caused by other, yet unknown, factors.