Objective: vitamin D is a potent immunomodulator.  A number of genetic polymorphisms in the vitamin D pathway have been shown to affect vitamin D signaling, and stratification according to such polymorphisms has already being implemented in randomized controlled clinical intervention studies. Aim of the work: the study was attempted to examine whether vitamin D improved viral response and predicted treatment outcome in patients with chronic hepatitis C virus (CHCV) infection. Patients and methods: ninety two patients with CHCV, whose age ranged between 20 and 56 years, were selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, before and after the treatment with pegylated interferon (PEG-IFN), ribavirin (RBV) and vitamin D supplementation drops; 2000 IU/day, 10 drops/day, six patients whom received identical therapy without vitamin D were included to serve as controls. All the patients had body mass index (BMI) ≤ 30, were subjected to the following: history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigations. CBCs and analysis of the expression of CYP 27 B1-1260 gene, vitamin D receptor (VDR), and the levels of serum 25-hydroxyvitamin D before and after chronic hepatitis C virus treatment. Results: the treatment group with vitamin D had BMI ≤ 30 and high viral load 90900004.00 IU/ML, (P= 0.098). Sixty three percent of treated patients were HCV RNA negative at 48 weeks after treatment (SVR). Baseline serum vitamin D level was 8.5 minimum, mean level (32.9 ± 27 ng/mL). It increased after 48 wk vit D treatment, to a mean level of (54.9 ± 38 ng/mL). VDR show highly significant difference between patients and controls as regarding Ff=55.4% for patients (P=0.01), and 66.7% ff for the controls (P=0.006) alleles. CYP27B1 show non significant relation   between   patients   and   controls, with   CYP27B1 genotype frequencies of the promoter polymorphism CC = 51.1% for patients, 66.7% for the control group, C allele frequency 69% for the patients, 83.3% for the controls, AC 35.9% for the patients, 33.3% for the controls. The majority of cases had A1F1 and A1F2 biopsy results.  Conclusion: our study suggests a role of vitamin D in the response to treatment of chronic HCV patients. However, serum concentration is not a suitable predictor of treatment outcome. VDR had a predictive positive treatment outcome. CYP27B1-1260 was found to be an independent predictor of sustained virologic response (SVR). Recommendations: The level of recommended supplementation of vitamin D depends on the patient's individual deficiency, although 2000 IU daily is a common dose. Patients taking vitamin D supplements should have serum measurements made after starting therapy to determine whether they are reaching target levels.