OBJECTIVES: To capture emerging, recurring, and evolving factors in HTA of new direct-acting antivirals in chronic hepatitis C. METHODS: We reviewed and undertook a thematic analysis of HTAs of daclatasvir, sofosbuvir, ledipasvir/sofosbuvir, and simeprevir from seven HTA agencies in five countries, published between May 2014 and January 2016. These agencies represented three payer archetypes: cost-effectiveness (NICE, SMC [UK]; CADTH [Canada]); comparative clinical effectiveness (TC [France], G-BA [Germany]); and budget impact (CAMHDA, GENESIS-SEFH [Spain]). A coding framework for payer concerns was based on a network of themes: burden of disease and unmet need, comparators, clinical trial quality, clinical benefit, safety, subgroups, indirect treatment comparisons, PROs, utilities, cost-effectiveness, budget impact and access schemes. RESULTS: Fifteen HTAs were identified: NICE (4), SMC (2), TC (1), G-BA (2), CADTH (2), CAMHDA (3), GENESIS-SEFH (1). A number of themes were identified: 4 global themes (product and disease context, clinical benefit, cost-effectiveness, budget impact), 11 organising themes (description of disease, product characteristics, SOC and comparator, eligible patient population, trial design, clinical benefit, resource use, costs, cost-effectiveness, budget impact, equity considerations), and 23 basic themes (unmet need, administration, innovation, mechanism of action, target patient population, place in treatment pathway, SOC and appropriate comparator, trial design, trial comparator, efficacy, safety, generalizability of clinical benefit, indirect treatment comparison, organizational impact, resource use, costs, cost-effectiveness model clinical inputs, cost-effectiveness analysis, model evaluation, utilities, uptake, budget impact, equity considerations). Basic themes in particular varied across payer archetypes, and over time. CONCLUSIONS: Thematic analysis is a strong method for understanding payer concerns and areas of focus – for a specific indication, over time, and over jurisdictions. The observed themes are based on a review of HCV medications therefore not all will be generalizable to other diseases. Themes around trial endpoints and survival analysis did not arise, but may with other indications (e.g., oncology).