Objectives To evaluate contraceptive and reproductive risk factors for cervical intraepithelial neoplasia (CIN) in southwestern American Indian women. Methods We conducted a clinic-based case-control study. Cases were American Indian women with biopsy-proven CIN I, CIN II or CIN III. Controls were from the same clinics and had normal cervical epithelium. All subjects underwent structured interviews focused on contraceptive and reproductive factors. Laboratory assays included polymerase chain reaction (PCR)-based tests for cervical human papillomavirus (HPV) infection. Results We enrolled 628 women in the study. The strongest risk factors for CIN II/III included HPV infection (adjusted odds ratio [OR] = 7.9, 95% CI:4.7-13.2), and low income (OR = 3.1, 95% CI : 1.7-5.7). The use of an intrauterine device (IUD) ever (OR = 3.0, 95% CI: 1.4-6.1) and currently (OR = 4.1, 95% CI: 1.1-14.6), and greater than or equal to3 vaginal deliveries (OR = 5.2, 95% CI:2.4-11.1) were associated with CIN II/III. History of infertility was also associated with CIN II/III (OR = 2.1, 95% CI: 1.0-4.2). Conclusions The data suggest that history of infertility, IUD use and vaginal deliveries were associated with CIN among American Indian women.