Most evidence on breast cancer screening accuracy derives from high income countries. We evaluated screening accuracy and factors related to program implementation in Bogota, Colombia. Between 2008 and 2012 participants underwent clinical breast examination (CBE) and mammography. Positive results underwent histological verification. Adherence to screening protocols was analyzed. Sensitivity, specificity, and predictive values were estimated and adjusted by overdiagnosis. Impact of alternative screening algorithms on follow-up was explored, including combined screening tests and modified coding systems for mammography. In total, 7436 women aged 50–69 were enrolled; 400 discontinued and 1003 non-compliant with screening protocols. 23 cancer cases were diagnosed. Mammography sensitivity and specificity were 78.3% (95%CI 77.3–99.3) and 99.4% (95%CI 99.2–99.6). CBE sensitivity was 39.1% (95%CI 37.9–40.3) and specificity 83.4% (95%CI 82.6–84.3). Parallel mammography and CBE showed the highest sensitivity (95.6%) and combined as serial tests the lowest (positive CBE followed by mammography 13.0%). A simplified coding system for mammography (recall/no-recall) had 6.3% of positive results and a minor reduction in specificity compared with standard mammography, but reported the best balance between recall rates and screening protocol compliance. Call-backs had high rates of loss-to-follow-up; thus, alternative screening algorithms might help increase screening compliance and follow-up in low and middle income countries, particularly in populations with poor screening history and low access to health services.