Introduction: The 2015 Centers for Disease Control Sexually Transmitted Diseases Treatment Guidelines recommend annual screening of all people living with HIV (PLWH) for Neisseria gonorrhoeae, Chlamydia trachomatis, and syphilis; annual Trichomonas vaginalis screening is recommended for HIV-infected women. The study objective was to evaluate the budgetary impact of sexually transmitted infection (STI) screening. We hypothesized that recommended STI screening is costly and would not be covered in full by insurers. Methods: This cost analysis evaluates charges and reimbursement for recommended screening for the above 4 STIs. This study projects the net yield (reimbursement minus expenditures) of providing tests to eligible PLWH receiving care at an urban HIV clinic in Birmingham, AL. Four scenarios evaluated the net yield when different laboratory providers, rates of compliance, and Ryan White Program fund availability were examined. Results: The number of patients receiving care at our HIV clinic from August 2014 to August 2015 was 3163 (768 female and 2395 male patients). Annual screening for N. gonorrhoeae, C. trachomatis, syphilis, and T. vaginalis would lead to a mean net loss of $129,416, $118,304, $72,625, and $13,523, respectively. Most costly scenarios for a health system include the use of a regional laboratory (-$1,241,101) and lack of Ryan White HIV/AIDS Program funding (-$85,148). Discussion: Compliance with STI screening practices is costly. Sustainability will require critical analysis of true costs and cost-effectiveness of STI screening tests in PLWH. Providers, policy makers, and insurers each have a role in ensuring the provision of these evidence-based services to PLWH.