High-sensitivity C-reactive protein (hs-CRP) has been shown to be linked with immune stimulation, but is not well studied over the lifetime in opiate addiction. hs-CRP was measured by standard laboratory methods in substance use disorder (SUD) patients and non-SUD (NSUD) aged 18-48 years. Data were log transformed to improve normality. 1231 SUD were compared with 326 NSUD patients of comparable ages. hs-CRP was 7.46 ± 14.24 versus 4.75 ± 13.40 mg/l (mean ± SD) significantly higher in the SUD group (P < 0.0001), a difference which persisted after exclusion of acutely elevated hs-CRP values (P < 0.0001). In multiple regression with age, addictive status was significant both by itself (P < 0.0001) and in interaction with age (P < 0.0001). At age 40 years, the SUD group had a mean hs-CRP of 3.68 which the NSUD group did not achieve till a modelled age of 157.09 years. In an interactive multivariate regression, interactions between age, addictive status, ALT and AST were significant. These data show that hs-CRP is elevated in opiate dependence both per se, and when controlled for age. Furthermore, they suggest that hs-CRP and immune stimulation seen in opiate addiction may underlie the acceleration of age-related multi-system chronic and coronary atherosclerotic disease well described in opiate dependence.