<b><i>Introduction:</i></b> Inflammation is important in the pathogenesis of atherosclerosis. Elevated interleukin-6 (IL-6) is associated with cardiovascular events and also predicts mortality in individuals with CKD. Our goal was to determine the association between IL-6, FGF23, and high-sensitivity C-reactive protein (hsCRP) on coronary artery calcification (CAC) progression and mortality in incident dialysis patients without prior coronary events. <b><i>Methods:</i></b> A prospective cohort of incident adult dialysis participants had CAC measured by ECG-triggered multislice CT scans at baseline and at least 12 months later. Lipids, mineral metabolism markers, FGF23, and inflammatory markers, such as IL-6 and hsCRP, were measured at the baseline visit. <b><i>Results:</i></b> Participants in the high IL-6 tertile had the highest baseline CAC score (133.25 [10.35–466.15]) compared to the low (0.25 [0–212.2]) and intermediate (29.55 [0–182.85]) tertiles. Almost half of the participants with high IL-6 (15 of 32 [46.9%]) experienced progression of CAC compared to participants with low (8 of 32 [25%]) and intermediate (9 of 32 [28.1%]) (<i>p</i> = 0.05) IL-6 levels. Each log increase in IL-6 was associated with increase in death (hazard ratio 2.2, 95% CI: 1.2–3.8; <i>p</i> = 0.01). After adjusting for smoking, age, gender, race, diabetes, phosphate, and baseline calcium score, IL-6 (log) was associated with 2.2 times (95% CI: 1.1–4.6; <i>p</i> = 0.03) increase in death. <b><i>Conclusion:</i></b> IL-6 is associated with progression of CAC and mortality in incident dialysis patients.