Epidemiological studies show that a high calcium intake reduces the risk of colon cancer. The objective was to study the association between calcium intake and colorectal neoplasia in a clinic-based sample of Hispanics adults from Puerto Rico. As part of this cross-sectional study, a total of 433 subjects were recruited from surgery and gastroenterology clinics at the University of Puerto Rico. Calcium intake was estimated using a food frequency questionnaire (FFQ) of calcium rich foods. Socio-demographics, health history and colonoscopy results were obtained from the primary study. Chi square and odds ratios (OR) for colorectal neoplasia (adenomas and/ or adenocarcinoma) were calculated for total calcium, dietary calcium and for calcium supplement use. In total, 312 (72%) from 433 participants completed the FFQ and had available colonoscopy results; from these, 196 (62.5%) were free of neoplasia and 117 (37.5%) had colorectal neoplasia. Colorectal neoplasia subjects were older, a lower proportion were females and less educated than those without neoplasia (p < 0.01). Total calcium intake (median 1180 mg/d) was greater in those free of neoplasia compared to colorectal neoplasia subjects (median 1036 mg/d; p<0.05). A high total calcium intake and the use of calcium supplements significantly reduced the OR (crude and age adjusted) for colorectal neoplasia; although these associations lost statistical significance after additionally adjusting for gender and educational level. In conclusion, a high calcium intake and the use of calcium supplements may be protective against colorectal neoplasia, although a greater sample may be required to observe significant associations in a multivariate model.