In patients with stable coronary artery disease, elevated levels of biomarkers of inflammation, including high-sensitivity C-reactive protein (hs-CRP) ≥2.0 mg/L, are predictors of future vascular events. Because long-term low-dose colchicine is a safe and effective means of dampening inflammation, we conducted an open-label pilot study to determine whether it could significantly lower hs-CRP in patients with stable coronary artery disease in whom hs-CRP was ≥2.0 mg/L despite taking both aspirin and high-dose atorvastatin therapy. Plasma hs-CRP was measured in 200 patients with clinically stable coronary artery disease who were taking aspirin and atorvastatin. In 64 patients, hs-CRP was ≥2.0 mg/L. In 20 of these patients, hs-CRP was measured again at 2 weeks (no treatment group), and in 44 patients, hs-CRP was measured again after 4 weeks of open-label colchicine 0.5 mg twice daily (treatment group). In the no treatment group, mean baseline hs-CRP did not decrease significantly, measuring 4.28 ± 2.03 mg/L at baseline and 3.70 ± 2.30 mg/L after repeated measurement (mean change 11.0%, 95% confidence interval [CI] −30% to +9%, p = NS). In contrast, hs-CRP decreased in all patients administered colchicine, with mean baseline hs-CRP decreasing from 4.58 ± 2.05 to 1.78 ± 1.38 mg/L (p <0.001), an absolute decrease of 2.80 mg/L (95% CI 2.40 to 3.65 mg/L) and a relative decrease of 60% (95% CI 54% to 67%). In 28 patients (64%) in this group, the decrease in hs-CRP was >50% from baseline, and in 31 patients (70%), hs-CRP decreased to <2.0 mg/L. No significant side effects were reported. In conclusion, low-dose colchicine (0.5 mg twice daily) can effectively decrease hs-CRP in patients with clinically stable coronary artery disease and increased hs-CRP independent of aspirin and atorvastatin use. Additional controlled studies are warranted to confirm this observation and determine whether long-term use of low-dose colchicine can improve clinical outcomes in patients with advanced vascular disease.