This study was undertaken to evaluate the prevalence of significant cervical pathology among women who are high-risk human papillomavirus (HR-HPV)-positive/cytology negative, the most common combination of positive co-tests. The records of 244 women HR-HPV-positive/cytology-negative who had undergone colposcopy at Srinagarind Hospital, Khon Kaen University during January 2010 and April 2014 were reviewed. Mean age was 46.4 years. Of these 224 women, 75 were positive for HPV types 16/18 (33.5%) and 123 were positive for non-16/18 types (54.9%). HR-HPV was not genotyped in the remaining 26 women (11.6%). Prevalence of significant lesions for the entire cohort was 2.4%, and 2.6% and 3.3%, respectively, for those with HPV 16/18 and other oncogenic HPV types. One woman with HPV 16/18 (1.3%) had invasive cervical cancer. Multiparous women were more likely to be infected with HPV 16/18 compared to nulliparous women (36.3% versus 17.6%, respectively). In conclusion, the prevalence of significant cervical lesion among our study population was 2.4%. Multiparous women were more likely to be infected with HPV 16/18 compared to nulliparous women.