Recent evidence demonstrates that individuals with low heart rate (HR) reactions to acute psychological stress are more likely to be obese or smokers. Smoking and obesity are established risk factors for increased carotid intima‐media thickness (IMT). The aim of this study was to examine the potential pathways linking intima‐media thickness, smoking, body mass index (BMI), and HR stress reactivity. A total of 552 participants, 47.6% male, M (SD) age = 58.3 (0.94) years, were exposed to three psychological stress tasks (Stroop, mirror drawing, and speech) preceded by a resting baseline period; HR was recorded throughout. HR reactivity was calculated as the average response across the three tasks minus average baseline HR. Smoking status, BMI, and IMT were determined by trained personnel. Controlling for important covariates (e.g., socioeconomic status), structural equation modeling revealed that BMI and smoking mediated the negative relationship between HR reactivity and IMT. The hypothesized model demonstrated a good overall fit to the data, χ2(8) = 0.692, p = .403; CFI = 1.00; TLI = 1.00 SRMR = .01; RMSEA < .001 (90% CI < 0.01–0.11). HR reactivity was negatively related to BMI (β = −.16) and smoking (β = −.18), and these in turn were positively associated with IMT (BMI: β = .10; smoking: β = .17). Diminished HR stress reactivity appears to be a marker for enlarged IMT and appears to be exerting its impact through already established risks. Future research should examine this relationship longitudinally and aim to intervene early.