Hepatitis C virus (HCV) infection remains a global health problem. Previously, the prevalence of NS5A resistance-associated substitutions (RASs) to elbasvir, a new direct-acting antiviral (DAA) against the NS5A viral protein was assessed by our group before its introduction into clinical use in Spain. However, the origin, epidemic history, transmission dynamics, diversity and baseline RASs to NS5A direct-acting agents of HCV-GT1a in Spain remain unknown. A nationwide cross-sectional survey of individuals chronically-infected with HCV-G1a and DAAs-naïve was performed. HCV population sequencing, phylogenetic analysis and Bayesian methods were used. GT1a clade II was more prevalent than clade I (82.3% vs. 17.7%; P < 0.001) and older (estimated origin in 1912 vs. 1952). Clade II epidemic is currently declining whereas clade I epidemic has reached equilibrium. A total of 58 single RASs were identified, which account for the moderate level (10%) of baseline resistance observed. When considering the regional data, marked differences were observed, with thirteen regions showing an intermediate level (5-15%) and one a high level (20%) of resistance. Current HCV-GT1a epidemic in Spain is driven by clade I which seem to have different dissemination routes relative to clade II. A moderate level of baseline RASs to NS5A-DAAs with marked differences among regions was observed. Close surveillance of response to treatment with DAAs will be important. Hepatitis C virus (HCV) infection is a global health problem with latest data estimates 71.1 million viraemic chronic infections (1.1% of world population) 1. HCV displays high genetic heterogeneity and is classified into eight major genotypes (1-8) 2 and 86 subtypes 3. Worldwide there are significant differences in epidemic history among the HCV genotypes (GT) which may differ in response to treatment, with GT1 being the most represented 4. Among HCV-infected patients also coinfected with human immunodeficiency virus (HIV) subtype 1a (GT1a) prevails 5-7. Despite the high rates of cure with the new direct-acting antivirals (DAAs), the presence of NS5A resistance-associated substitutions (RASs) may compromise the efficacy of NS5A inhibitors. Recently, Zeuzem and colleagues (2017) observed that pretreatment ledipasvir-specific RASs (identified in 8-16% of patients) may compromise treatment outcome particularly in treatment-experienced patients with GT1a, as they found a sustained virological response (SVR) rate of only 76% in patients with pretreatment RASs 8. The seroprevalence of HCV infection in Spain is 1.1% 9 and hepatitis C leads the list of infectious disease related mortality 10. GT1 accounts for 67% of all HCV infections and GT1a causes 40% of all GT1 infections 11. Until October 2018 117,452 patients had access to DAAs and 95.5% had SVR in the frame of the national plan of universal access to treatment 12 while 1.1% of those cured are reinfected 7 .