Background: Colposcopy diagnosis and directed biopsy are the key components in cervical cancer screening programs. However, their performance is limited by the requirement for experienced colposcopists. This study aimed to develop and validate a Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) for grading colposcopic impressions and guiding biopsies. Methods: Anonymized digital records of 19,435 patients were obtained from six hospitals across China. These records included colposcopic images, clinical information, and pathological results (gold standard). The data were randomly assigned (7:1:2) to a training and a tuning set for developing CAIADS and to a validation set for evaluating performance. Results: The agreement between CAIADS-graded colposcopic impressions and pathology findings was higher than that of colposcopies interpreted by colposcopists (82.2% versus 65.9%, kappa 0.750 versus 0.516, p < 0.001). For detecting pathological high-grade squamous intraepithelial lesion or worse (HSIL+), CAIADS showed higher sensitivity than the use of colposcopies interpreted by colposcopists at either biopsy threshold (low-grade or worse 90.5%, 95% CI 88.9–91.4% versus 83.5%, 81.5–85.3%; high-grade or worse 71.9%, 69.5–74.2% versus 60.4%, 57.9–62.9%; all p < 0.001), whereas the specificities were similar (low-grade or worse 51.8%, 49.8–53.8% versus 52.0%, 50.0–54.1%; high-grade or worse 93.9%, 92.9–94.9% versus 94.9%, 93.9–95.7%; all p > 0.05). The CAIADS also demonstrated a superior ability in predicting biopsy sites, with a median mean-intersection-over-union (mIoU) of 0.758. Conclusions: The CAIADS has potential in assisting beginners and for improving the diagnostic quality of colposcopy and biopsy in the detection of cervical precancer/cancer. © 2020, The Author(s).