High dosage and longer duration of antiviral treatment has been suggested to treat cryoglobulinemia patients. We aimed to investigate the efficacy of antiviral treatment in cryoglobulinemia patients and analyze the associated factors of persistent cryoglobulinemia. Totally 148 patients after completion of anti-HCV treatment were enrolled in our study. Serum cryoglobulinemia precipitation was assessed and analyzed for the associated factors after antiviral therapy. Fifty-one (34.5%) out of 148 patients were positive for serum cryoglobulinemia after completion of antiviral therapy. In multivariate analysis, advanced fibrosis (Odds Ratio OR- 4.13, 95% Confidence Interval 95% CI- 1.53-11.17, p = 0.005) and platelet counts (OR-0.98, 95% CI- 0.97-0.99, p = 0.010) were independently and significantly associated with persistent cryoglobulinemia. The factors associated with the persistent cryoglobulinemia in SVR patients were advanced fibrosis (OR-1.93, 95% CI- 1.02-3.65, p = 0.041) and platelet count (OR-0.98, 95% CI- 0.96-0.99, p = 0.041) by multivariate analysis. Multivariate logistic regression analysis showed persistent (OR-4.83, 95% CI- 1.75-13.36, p = 0.002) was significantly associated with advanced fibrosis in patients with cryoglobulinemia follow up after antiviral therapy. The prevalence of the persistent cryoglobulinemia is 34.5% after completing antiviral therapy and it is associated with advanced fibrosis, also HCV clearance.