Sexually transmitted infections (STI) can have severe consequences. In Brazil, case management is recommended by the Clinical Protocol and Therapeutical Guidelines for Comprehensive Care for People with STIs (PCDT-IST). This study assessed the quality of PCDT-IST (2021) and reviewed the main recommendations for the management of STI that cause urethral discharge compared with the World Health Organization (WHO) STI Guidelines. The PCDT-IST (2021) quality was independently assessed by 4 appraisers using the Appraisal of Guidelines Research and Evaluation instrument, version II (AGREE II). The PCDT-IST (2021) and the WHO Guidelines for the Management of Symptomatic STI (2021) were compared considering 14 different assessment domains. The PCDT-IST (2021) scores in the AGREE II domains were: Rigor of Development (58%), Applicability (35%), Editorial Independence (38%), Scope and Purpose (78%), Stakeholder Involvement (74%), and Clarity and Presentation (82%). The overall score was 67%, and all appraisers recommended the Brazilian guideline. Regarding the PCDT-IST (2021) and the WHO STI Guidelines (2021) comparation, 10 domains would be relevant for further reviewing the Brazilian recommendations: Diagnostic tests; Etiological approach; Treatment for recurrent urethral discharge; Treatment for urethritis without etiological agent identification; Treatment for gonococcal urethritis; Treatment for chlamydial urethritis; Retreatment for gonococcal infections; Treatment for Mycoplasma genitalium urethritis; Treatment for Trichomonas vaginalis urethritis; 10. Flowcharts. The PCDT-IST (2021) has a reasonable degree of quality. However, the domains of Applicability, Rigor of Development, and Editorial Independence must be better ensured. The guidelines comparison will help to select key topics that should be addressed with priority in the following national STI guidelines updates.