Both active smoking and exposure to secondhand smoke (SHS) are associated with cardiovascular disease, but sidestream smoke contains higher levels of small particles and toxic gases than mainstream smoke. The relationship between the concentration of cotinine and a number of cardiovascular biomarkers among nonsmokers and active smokers was examined. A cross-sectional study using the Scottish Health Surveys conducted between 1998 and 2010 was undertaken. Inclusion was restricted to participants aged ≥16 years who had provided saliva and blood samples. Uni- and multivariate regression models were used to examine the relationships between the concentration of cotinine and C-reactive protein (CRP), high-density lipoprotein (HDL) cholesterol, and fibrinogen concentrations, as well as total:HDL cholesterol ratios. Of the 10,018 eligible participants, 7,345 (73.3%) were confirmed to be nonsmokers (cotinine <15.0 ng/mL) and 2,673 (26.7%) were confirmed to be current smokers (cotinine ≥15.0 ng/mL). CRP and total:HDL cholesterol increased, and HDL cholesterol decreased, with increasing cotinine concentration across nonsmokers and smokers (all p < .001). However, there were step changes at the interface, whereby nonsmokers with a high exposure to SHS had lower concentrations of cotinine than light active smokers but comparable concentrations of CRP (p = .709), HDL cholesterol (p = .931), and total:HDL cholesterol (p = .405). Fibrinogen concentrations were significantly raised in moderate and heavy active smokers only (both p < .001). Exposure to SHS is associated with disproportionately higher biomarkers of cardiovascular risk compared with active smoking. Protection from exposure to SHS should be a public health priority.