BackgroundSexually transmitted infections (STIs) include a group of clinical syndromes that can be transmitted mainly through sexual activity. Using STIs' syndromic approach for diagnosis and management is widely recommended to control and reduce the burden of these transmissible diseases. ObjectiveThe objective of this article is to assess the knowledge and practice of physicians concerning syndromic management of STIs in National Guard Primary Health Care (PHC) centers in Jeddah city, Saudi Arabia. Materials and methodsThis observational study was conducted at the National Guard PHC centers in Jeddah City, Saudi Arabia. An interview-administered questionnaire was designed. Fifty physicians have met the inclusion criteria, and all of them were included in the present study. ResultsOf the study population, 47 PHC physicians (response rate was 94%) were interviewed and the questionnaire was completed. Overall, the physicians' knowledge was different from one syndrome to another; it was highest for urethral discharge (72%) and lowest for vaginal discharge in pregnant women (21%). During the last 10 days, the physicians in the present study reported that two-thirds of their cases of STI were urethral discharge cases. However, during the previous 10 days, the practice assessment revealed that most physicians (76%) were correctly prescribed the medications as indicated by specific patients' syndromes. ConclusionSyndromic management is essential guidance to control and reduce the burden of STIs. Overall knowledge and practice of physicians were different from one syndrome to another. There is a need to design continuing medical education programs targeting PHC physicians to be clinically and culturally competent against socially sensitive diseases like STIs.