INTRODUCTION: Use of combined contraceptive vaginal ring (CCVR) has been found to upregulate immune-related genes in the endocervix and mediators within the cervicovaginal fluid. Attachment and infection rates of certain pathogens within this tract can vary based on hormones within the local environment. Rat studies have shown treatment with estrogen prior to chlamydial infections was protective. Continued clinical safety analyses are critical as CCVR use continues to increase. We calculated risk of vaginal infections associated with CCVR compared to oral contraceptive pills (OCPs) via retrospective chart review. METHODS: De-identified data was collected from TriNetX. Using ICD-10 and RxNorm codes, study cohorts included women receiving etonogestrel and ethinyl estradiol CCVRs without segesterone, versus women on OCPs without vaginal hormones. Cohorts (n=30,796 each) were matched for age, race, and ethnicity. Statistical analysis within 1 year of CCVR placement used risk ratios (RRs); P<.05 was considered significant. RESULTS: Combined contraceptive vaginal rings showed increased risk of HSV-2 (RR 1.790; P<.0005), acute vaginitis (RR 1.722; P<.0005), subacute/chronic vaginitis (RR 1.904; P<.0005), subacute/chronic vulvitis (RR 1.969; P<.0005), acute vulvitis (RR 1.894; P<.0005), candidiasis (RR 1.464; P<.0005), trichomoniasis (RR 2.162; P<.0005), and pelvic inflammatory disease (PID) (RR 2.984; P<.0005). Combined contraceptive vaginal rings showed a decreased risk of chlamydia (RR 0.760; P=.047). There were no differences in risk of gonorrhea, syphilis, HIV, or anogenital warts between the CCVR and OCP cohorts CONCLUSION: In this chart review, women using CCVRs had increased risks for HSV-2, vaginitis, vulvitis, PID, trichomoniasis, and candidiasis and decreased risk of chlamydia compared to OCPs. Further study of local hormone delivery on the vaginal mucosa is warranted.