OBJECTIVES: To examine differences in annual healthcare utilization associated with three treatment regimens: fixed dose combination of ledipasvir and sofosbuvir (LS); peginteferon, ribavirin and sofosbuvir (PRS); and simeprevir and sofosbuvir with/without ribavirin (SSR) for patients with genotype I chronic hepatitis C virus (CHCV). METHODS: This observational study used propensity score methods to identify suitable comparison groups in a large nationally representative claims database. The sample consisted of CHCV patients aged 18+ who had a new prescription fill (index) for LS, PRS, or SSR between 2014 and 2015. Patients had to be continuously enrolled in a plan with pharmacy and medical coverage for at least 6 months before and 1 year after treatment initiation. Patients with a diagnosis of a serious medical condition at baseline were excluded. A two-part model was estimated separately for emergency room (ER) visits, ambulatory services, and hospitalizations: 1) a logit model for estimating the differences in the likelihood of having utilization among the three treatment regimens; and 2) a negative binomial model for estimating the differences in the level of utilization among non-zero users. RESULTS: A total of 2,615 CHCV patients were identified for the sample. Compared to patients treated with PRS, after controlling for potential confounders, those with LS had a significantly lower likelihood of being hospitalized (OR=0.639, 95% CI: 0.447-0.913), having ER visits (OR=0.673, 95% CI: 0.534-0.848) and having ambulatory services (OR=0.344, 95% CI: 0.233-0.509). Patients with SSR had a significantly lower likelihood of being hospitalized than those with PRS (OR=0.859, 95% CI: 0.853-0.864). Among patients who had ambulatory services, those with LS had significantly fewer numbers of services than those with PRS. CONCLUSIONS: This study suggests that sofosbuvir-related treatments without peginterferon are associated with reduced likelihood of being hospitalized. Quasi-experimental studies or randomized clinical trials can address the issue of spillover effect and secular trends.