This study was undertaken to evaluate the prevalence of underlying significant lesions among women referred for colposcopy after atypical glandular cell (AGC) smears and the associated risks. The present study reviewed data from women with AGC smears undergoing colposcopy at the Colposcopy Clinic, Faculty of Medicine, Khon Kaen University, Thailand between January 2001 to December 2014. Significant lesions included cervical intraepithelial neoplasia grade 2-3, adenocarcinoma in situ, endometrial hyperplasia, and cancer. During the study period, 170 women with AGC cytology were reviewed. The mean age was 45.7 years. Thirty-eight women (22.4%) were postmenopausal. Eighteen smears (10.6%) were further subclassified as AGC-favor neoplasia (AGC-FN). In total, significant lesions were noted in 27 women (15.9%; 95%CI, 7.8%-18.3%). Thirteen women (7.6%, 95%CI, 4.1%-12.7%) were found to have cervical cancer or endometrial cancer. Two variables were independently associated with an increased risk of significant histopathology results: level of educational attainment (secondary level or lower versus bachelor degree or higher) and types of AGC (AGC versus AGCFN). Women who had low level of education and those with AGC-FN were at the higher risk of significant lesions (OR, 3.16; 95%CI 1.10-9.11 and OR, 4.62; 95%CI, 1.54-13.85, respectively). In conclusion, the rate of significant lesions among women referred for colposcopy after AGC smears is considerably high. Low education and smear subtypes appear independently associated with a higher risk of significant lesions.