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Sexually transmitted infections (STIs) are major infectious diseases worldwide. Around one million people get STIs every day and among them a high burden of the diseases seen in Sub-Saharan African countries. In most developing countries, including Ethiopia, STIs are diagnosed only using syndromic methods, although there seems to be no consensus between syndromic and laboratory-based research.To compare the effectiveness of a syndromic versus laboratory-based approach in the diagnosis of sexually transmitted infections, especially Neisseria gonorrhoeae (NG) and Treponema palladium (TP), infections among those attending a public health center in Addis Ababa, Ethiopia.a cross-sectional study was conducted from April 2019 to March 2020, at selected health centers STIs clinics in Addis Ababa, Ethiopia. A total of 325 study participants were involved. From each participant after having socio-demographic data, additional blood, urethral and vaginal discharge was collected. Then serological, Gram stain, culture, and biochemical tests were performed. SPSS version 23 was used to enter and analyze data. All relevant bodies provided ethical approval, and each study participant gave written informed consent.Among the total participants 167 (51.4%) were males; 177 (54.5%) between ages of 26 and 35; and 178(54.8%) single. Of the total 325 NG, and 125 TP syndromic managed suspected cases, only 163 (50%) and 38 (30.4%) were laboratory- confirmed positive cases respectively. However, there was no statistically significant difference between NG and TP syndromic versus laboratory diagnostic confirmed cases (P-value 0.005).The present study indicated that even if, there were no statistical differences between syndromic versus Laboratory diagnosis confirmed NG and TP cases, more than half of syndromic cases could not be confirmed by laboratory diagnosed tests. Thus, to strengthen the present findings, further large-scale studies are recommended.Sexually transmitted infections (STIs) are the leading infectious diseases worldwide, and the majority of cases are recorded in developing countries, including Ethiopia. However, diagnosis of STIs in most developing countries done syndromic based, since the laboratory-based tests are relatively expensive, need skilled manpower, and time taking. Therefore regular assessments on how closely related STIs syndromic versus laboratory-based diagnosis should be done, for the proper management of the diseases. In this regard, the present study demonstrated that there was no statistically significant difference between syndromic versus laboratory-based diagnosis of some certain STIs infections; Neisseria gonorrhoeae (NG) and Treponema pallidum (TP), in selected public health centers in Addis Ababa, Ethiopia. However, more than half of syndromic cases could not be confirmed by laboratory diagnosed tests. Thus, to narrow the gap between the two diagnostic approaches, regular training, updates, and similar studies need to cascade in the country. In the meantime, in other developing countries too, regular assessment on STIs syndromic versus laboratory-based diagnosis should be done, to control and prevent STIs infections worldwide.