Introduction Antineutrophil cytoplasmic antibodies (ANCA) testing is a screening method that may be applied in clinical practice. Testing for vasculitis linked to antineutrophil cytoplasmic antibodies (AAV) usually involves these measurements. ANCAs are not exclusive to vasculitis; immunofluorescence testing can also detect (atypical) ANCA patterns in other inflammatory diseases. As a result, using indirect immunofluorescence (IIF) in addition to an immunoassay was advised. These discoveries led to the establishment of a new worldwide consensus. The 2017 international agreement on ANCA testing states that when immunoassay is used as the primary screening method to detect AAV, IIF should not be necessary. Aim Assess the efficacy of the suggested method for ANCA detection based on antigen-specific immunoassay screening. A number of patients with AAV and relevant disease controls, meaning patients for whom ANCA was ordered in relation to small-vessel vasculitis, will be evaluated. These patients may include those with infections, illnesses produced by drugs, connective tissue disease, etc. Results Regarding the respiratory features among the two studied groups (ANCA vasculitis group and non-ANCA vasculitis group), it was found that cough with fever (p = 0.024), pulmonary hemorrhage (p = 0.024), interstitial lung disease (ILD) (p = 0.024), pulmonary renal syndrome (0.001), and pleural thickening (p = 0.024) were the most common and the leading clinical manifestation that differentiate between ANCA and non-ANCA vasculitis. Also, in studying different extra pulmonary system features between the two clinical groups for differential diagnosis, it was found that rash (p = 0.001), dry mouth (p = 0.001), bloody diarrhea (p = 0.024), bilateral scleritis (p = 0.024), and vision loss (p = 0.001) were the most clinically leading symptoms Moreover, the laboratory parameters among the two clinically suspected vasculitis groups were in favor of vasculitis if proteinase-3 (pr3) ANCA (p < 0.001) and or the myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO) ANCA (p = 0.001) or the patient had proteinuria and hematuria. Regarding the diagnostic performance of different biomarkers to detect ANCA, it was found that at level > 1.5, the sensitivity of pr3 ANCA is 99.9% and the specificity is 92%, while at level > 3, the sensitivity of MPO ANCA is 90% and the specificity is 55%. Conclusion The investigation's findings support the global European consensus reached in 2017 that anti-PR3 and anti-MPO immunoassay should be used for first screening for ANCA-associated vasculitis instead of ANCA testing by IIF. Similar levels of specificity and sensitivity were shown by immunoassays employing direct, capture, and anchor. A positive anti-PR3 test would be very helpful when granulomatosis with polyangiitis (GPA) is suspected, and an anti-MPO might be used to diagnose MPA.