The Chronic Spontaneous Urticaria (CSU) is a common and distressing skin condition that causes red , raised , itchy and sometimes painful hives or wheals (raised rash or patches ) on the skin without known obvious trigger. It present daily for at least six weeks and is referred to as spontaneous when symptoms are not triggered by a known cause. The CSU is an unpredictable and debilating condition which can affects daily life in many ways, including sleep deprivation , anxiety and social isolation. Due to the lack of literature on CSU at the population level, proximal treatment algorithms are developed in limited resource countries. In this pragmatic approach, many studies have explored such treatment and challenges worldwide. The current study makes an effort to show the safety and effectiveness of autologous serum therapy in autologous serum therapy (+ve) and (-ve) groups in this setting. 200 (autologous serum therapy +ve and -ve) CSU known patients were administered autologous serum therapy in various time intervals (from the baseline to the eighth week). Each follow-up patient was closely observed, and any adverse events (safety and efficacy) were recorded. The Dermatologic Life Quality Index and the Urticaria Activity Score (UAS) were used to evaluate all patients (DLQI). According to the findings, there were substantial improvements in the UAS-7 and DLQI at the eight and twelfth weeks (P=0.001). Mild erythema and pain at the injection site were the only unfavourable reactions seen (9%) in participants overall, with strong specificity (98.11%), sensitivity (89.56%), PPV (75.42), NPV-(71.24), accuracy (80.52), and odds ratio (>1). In conclusion, many patients may benefit from this more recent medication, which has been proved to be more effective and safe.