Background: Aged garlic extract (AGE) and coenzyme Q10 (CoQ10) have been shown to affect multiple cardiovascular risk factors. The current study evaluates the effect of AGE combined with CoQ10 on inflammatory markers and progression of coronary atherosclerosis compared with placebo. Methods and Results: In this placebo-controlled, double-blind, randomized trial, 65 intermediate risk firefighters (age 55 ± 6 years) were treated with a placebo capsule or a capsule containing AGE and CoQ10 (AGE+CoQ10, 1200 and 120 mg, respectively) daily for 1 year. All participants underwent coronary artery calcium (CAC) scanning and C-reactive protein (CRP) at baseline and at 12 months. At 1 year, mean CAC progression was significantly lower in AGE+CoQ10 (32 ± 6 vs. 58 ± 8, P = 0.01) than placebo. Similarly, CRP were significantly decreased in AGE+CoQ10 compared with placebo (-0.12 ± 0.24 vs. 0.91 ± 0.56 mg/L, P < 0.05). After adjustment for age, gender, conventional cardiac risk factors, and statin therapy, AGE+CoQ10 was associated with 3.99 fold (95% 1.3–12.2, P = 0.01) lack of CAC progression compared with the placebo. Conclusion: AGE+CoQ10 are associated with beneficial effects on inflammatory markers and reduced progression of coronary atherosclerosis.