Gonorrhea (NG) and chlamydia (CT) are frequently diagnosed sexually transmitted infections (STIs) in the emergency department (ED). Results of nucleic acid amplification tests (NAATs) are not available at the time of the clinical encounter requiring providers to decide whether to treat the patient in the ED or wait for the NAAT results to come back. Not treating the patient in the ED risks the ED not being able to reconnect with the patient for treatment if the NAAT is positive. Clinical gestalt about who has a STI is poor leading clinicians to significantly over-treat patients for STIs when none exists as well as miss those with the disease. The objectives of our study were to determine the variables associated with NG and CT infection in the ED. We reviewed 17,358 female and 1,119 male encounters where testing was performed for NG and/or CT in EDs in northeast Ohio between 2012 and 2017. We performed Chi-square analysis or t-tests using data obtained at triage including demographic information, mechanism of ED arrival, ED disposition, ED length of stay, pain level, ICD-9 and ICD-10 codes, and the vaginal wet prep, STI testing, urinalysis, and urine culture results to identify the independent variables associated with having NG and/or CT. An alpha 0.05 was sent for statistical significance. In our cohort 9.8% (1703) of females and 6.9% (759) of males were positive for NG and/or CT by NAAT. The following variables were significantly associated being infected for NG and/or CT in females: younger age, black race, unmarried, Medicaid insurance, higher emergency severity index (ESI), no primary care physician, pregnant, infected with Trichomonas vaginalis, lack of yeast but the presence of clue cells on vaginal wet prep. Additionally, on urinalysis there were positive associations between leukocyte esterase, white blood cell (WBCs), WBC clumps, nitrite, protein, urine red blood cells (RBCs), amorphous crystals, and not having glucose in the urine. For men the following variables were significantly associated with being infected with NG and/or CT: younger age, black race, unmarried, higher ESI, WBC on penile wet prep, and on urinalysis: higher WBCs, positive leukocyte esterase, WBC clumps, mucus, proteinuria, urine bacteria, urine RBCs, urobilinogen, and lack of glucose. Univariate analysis shows multiple independent variables significantly associated with both NG and/or CT infection in males and females in the ED. Clinicians’ decisions regarding treatment for STIs in the ED inherently rely on a form of Bayesian analysis because definitive test results are not available at the time of the clinical encounter. No validated clinical decision rules regarding treatment of STI in the ED have yet been developed. The independent variables identified in our analysis can be utilized for future multivariate analysis to help create clinical decision tools to aid clinicians caring for persons being evaluated for STIs.