Inflammation and oxidative stress play important roles in colorectal carcinogenesis. There is strong evidence that calcium reduces risk for colorectal neoplasms, possibly through its ability to bind bile acids and prevent their colonic toxicity (which occurs via an oxidative mechanism and results in an inflammatory response). In a previously reported pilot, randomized, controlled trial among sporadic colorectal adenoma patients we found that those on 2.0 g/day of calcium, relative to those on placebo, had an estimated drop in a combined cytokine z-score of 48% (P = 0.18) over 6 months. To followup these promising preliminary findings, we tested the efficacy of two doses of supplemental calcium (1.0 or 2.0 g/day) relative to placebo on modulating circulating biomarkers of inflammation [C-reactive protein (CRP) and 10 cytokines] and oxidative stress (F2-isoprostanes) over a 4-month treatment period among 193 patients with previous sporadic, colorectal adenoma in a randomized, double-blinded, placebo-controlled clinical trial. The inflammation markers were measured in plasma using electrochemiluminescence detection-based immunoassays, and F2-isoprostanes were measured in plasma using gas chromatography-mass spectrometry. Over a 4-month treatment period, we found no appreciable effects of calcium on CRP, cytokines, or F2-isoprostanes (P > 0.4), overall or within strata of several major risk factors for colorectal carcinogenesis, such as body mass index and regular use of nonsteroidal anti-inflammatory drugs. Overall, our results provide no evidence that calcium supplementation favorably modulates concentrations of circulating biomarkers of inflammation or oxidative stress over 4 months among patients with a previous colorectal adenoma.