Abstract Background: Low-income African American women face numerous barriers to mammography screening. We tested the efficacy of a combined interactive computer program and lay health advisor intervention to increase mammography screening. Methods: In this randomized, single blind study, participants were 181 African American female health center patients of ages 41 to 75 years, at ≤250% of poverty level, with no breast cancer history, and with no screening mammogram in the past 15 months. They were assigned to either (a) a low-dose comparison group consisting of a culturally appropriate mammography screening pamphlet or (b) interactive, tailored computer instruction at baseline and four monthly lay health advisor counseling sessions. Self-reported screening data were collected at baseline and 6 months and verified by medical record. Results: For intent-to-treat analysis of primary outcome (medical record–verified mammography screening, available on all but two participants), the intervention group had increased screening to 51% (45 of 89) compared with 18% (16 of 90) for the comparison group at 6 months. When adjusted for employment status, disability, first-degree relatives with breast cancer, health insurance, and previous breast biopsies, the intervention group was three times more likely (adjusted relative risk, 2.7; 95% confidence interval, 1.8-3.7; P < 0.0001) to get screened than the low-dose comparison group. Similar results were found for self-reported mammography stage of screening adoption. Conclusions: The combined intervention was efficacious in improving mammography screening in low-income African American women, with an unadjusted effect size (relative risk, 2.84) significantly higher (P < 0.05) than that in previous studies of each intervention alone. Cancer Epidemiol Biomarkers Prev; 19(1); 201–10