The MINMON trial examined efficacy and safety of a minimal monitoring strategy for delivering HCV treatment to a diverse, global population of treatment-naïve participants. 400 HBsAg-negative adults seen at infectious disease clinics—most affiliated with universities—in Brazil, South Africa, Thailand, Uganda, and the U.S. were staged based on FIB-4 index (no pre-treatment HCV genotype assessment was performed): compensated cirrhosis was defined as FIB-4 ≥ 3.25 and Child-Pugh score ≤ 6. Enrollment occurred between October 2018 and July 2019: over 40% of participants were living with HIV (99% were receiving suppressive non-efavirenz based ART). 12 weeks of sofosbuvir/velpatasvir was dispensed at study entry, and no scheduled clinic or laboratory monitoring visits were conducted before the 24-week efficacy outcome assessment. Remote contact occurred at: (a) week 4 to assess adherence, and (b) week 22 to schedule outcome assessment visit (participant contact information was updated at both points). 91% of participants self-reported completing all study medications at the expected 84-day timepoint (+/- 1 week). 89% reported taking 100% of medications within the treatment period and 8% reported taking 90-99%. Overall, 95% experienced SVR: subgroup analyses indicated lower SVR rates among participants with cirrhosis (88.2% vs. 95.6%), participants < 30 years of age (84.8% vs. 95.9%), and participants with genotype 3. SVR was > 94% for participants with current or previous history of substance use. 4% experienced at least one serious adverse event, and 6% experienced non-serious events: 5 cases of non-serious events were attributed to study medication.