The purpose of this study was to examine short-term longitudinal relationships between handgrip strength (HGS) and cardiovascular disease (CVD) biomarkers in middle-aged to older adults living in rural areas (N = 138). The association between HGS and CVD biomarkers was examined at baseline, with HGS as a predictor of the annual change in biomarkers, and in a parallel fashion between the annual change in HGS and CVD biomarkers over an average of 2.8 follow-up years. The results showed HGS to cross-sectionally associate with waist circumference and diastolic blood pressure at baseline, but HGS at baseline was not found to predict the annual change in any biomarker. The annual increase in HGS was significantly associated with favorable changes in high-density lipoprotein cholesterol, triglycerides, and systolic/diastolic blood pressures; yet, these associations varied by the baseline levels of biomarkers. The present findings suggest that improved muscle strength with aging is related to favorable changes in CVD biomarkers.