Background Persistent synovitis (PS) may lead to erosive joint damage and result in functional disability. Objectives The aim of the study was to identify the risk factors for development of PS in early undifferentiated arthritis patients (EUA) attending Al Sharqia Governorate Hospitals, Egypt. Patients and methods A total of 80 EUA patients comprised the patients group. Assessment was performed twice (baseline and after 1 year) using clinical, laboratory, functional, and radiological [high resolution ultrasonography (HRUS) and power Doppler (PD)] assessments. Results Among 80 patients assessed, 20 (25%) showed evidence of self-limiting arthritis and 60 (75%) had PS (PS):16 (27%) developed rheumatoid arthritis, 14 (23%) progressed to spondyloarthropathy, and 30 (50%) remained undifferentiated (UA). Baseline tender and swollen Joint Counts (TJC and SJC) and anti-CCP2 titer were significantly evident in PS patients. Baseline HRUS total score of synovitis and PD total score were significantly higher in PS patients. Family history of any specific rheumatic disease, SJC, anti-CCP2 titer, HRUS total synovitis score, and PD total score were the significant risk factors of PS development. The most significant risk factor of PS (logistic regression analysis) was the baseline PD total score. Conclusion Baseline PD total score is the most significant risk factor for development of PS in EUA patients. Recommendation PD examination of all patients presenting with EUA should be performed.