Background: Hepatitis C represents a major health problem worldwide as it is the leading cause of liver cirrhosis and hepatocellular carcinoma. Additionally, it is mostly asymptomatic, leads to its diagnosis in late stages. Objectives: To estimate the prevalence and identify determinants of Hepatitis C infection among high-risk patients referred from Primary Health Care Centers (PHCCs) to specialized Primary Health Care Centers of Hepatitis C. Design: Analytical cross-sectional study. Setting: Specialized primary health care centers of Hepatitis C in Makkah Al-Mokarramah. Patients and Methods: most of the high-risk patients who visited Hepatitis C screening clinics were involved, A self-administered questionnaire was validated and used for data collection. Main outcome measures: sociodemographic data, comorbidities, and risk factors of Hepatitis C infection via questionnaire. Sample Size: 83 Participants. Results: The participants' age ranged between 20 and 75 years with a mean standard deviation (SD) of 50.8±13.7 years. More than half of them (52.4%) were males. The prevalence of Hepatitis C infection among the participants was 4.8%. Older (p=0.048), divorced/widowed participants (p=0.018), diabetic patients (p=0.043), participants who had other chronic diseases (p=0.036), participants with a history of hospital admission (p=0.050), history of blood transfusion (p<0.001) being a prisoner (p=0.010) and those with history of liver diseases (p<0.001) were at higher risk for hepatitis c viral infection. Conclusion: Hepatitis C viral infection is relatively more prevalent among high-risk patients, referred from primary health care centers to specialized primary health care centers of Hepatitis C in Makkah Al-Mokarramah, than the general population with some identified risk factors. Limitation: short duration of data collection and limited Hepatitis C screening clinics in Makkah Al-Mokarramah as there were 4 clinics, each working one day per week. Conflict of interest: None