Objective To analyze the risk factors of persistent infection of high-risk human papillomavirus (HR-HPV) after cervical conization, so as to identify the high-risk population of residual and recurrent cervical lesions after cervical conization. Method A total of 467 patients with one more HR-HPV infection and underwent cervical conization in the outpatient clinic and ward of our hospital from January 1,2017 to May 31,2022 were collected. After cervical conization,HR-HPV-positive patients within 6 months were included in the HR-HPV persistent infection group, and HR-HPV-negative patients were included in the HR-HPV clearance group. The differences in age, menopausal status, preoperative HR-HPV infection, preoperative thinprep cytologic test (TCT), pathological grade of cervical biopsy, conization margin status, glandular involvement, and conization surgery were compared between the two groups. Among them, the age difference was processed by rank sum test, and other indicators were compared by chi-square test. Multivariate Logistic regression analysis was used to find the high risk factors for HR-HPV persistent infection after cervical conization. Result The HR-HPV clearance rate was 64.0% within 6 months after cervical conization. Patients with age ≥ 46 years old (P<0.001 ), menopause (P<0.001), preoperative infection of any type of HPV 16, HPV 52 or HPV 58 (P=0.002), preoperative multiple HPV infection (P<0.001), preoperative TCT < high grade squamous intraepithelial lesion (HSIL) (P=0.005), cervical biopsy pathology < HSIL (P=0.020), unclean margin (P=0.003), gland involvement (P=0.008) or loop electrosurgical excision procedure (LEEP) (P<0.001), had a higher probability of HR-HPV persistent infection after cervical conization. Multivariate Logistic regression analysis showed that menopause (OR=3.453, P<0.001), preoperative HR-HPV multiple infection (OR=2.683, P<0.001), preoperative TCT < HSIL (OR=1.884, P=0.015), unclean margin (OR=1.479, P=0.048) and LEEP (OR=2.330, P=0.013) were independent risk factors for HR-HPV persistent infection after cervical conization.The residual and recurrence rate of cervical lesions at 6-24 months after conization was 12.2%. Compared with HR-HPV clearance group, HR-HPV persistent infection group had a higher rate of residual and recurrent cervical lesions at 6-24 months after cervical conization (28.6% vs 3.0%, χ²=65.585, P<0.001), and the risk of HSIL was also higher (Fisher test, P=0.027). Conclusions In this study, a large sample size is included, and menopause, preoperative HR-HPV multiple infection, preoperative TCT < HSIL, unclean margin, and LEEP are identified as high-risk factors for HR-HPV persistent infection after cervical conization, and a higher risk of residual and recurrent cervical lesions (especially HSIL lesions) after cervical conization.