Background Finding a suitable treatment for HCV patients with swallowing disorders is still a major challenge. In practice, direct-acting antivirals are crushed without knowledge of adequate absorption. Crushing can alter drug exposure, possibly leading to treatment failure, development of resistance or toxicity. Currently, there is no information about crushing of the fixed-dose combination tablet of elbasvir/grazoprevir; therefore, crushing of this tablet is not recommended. Objectives To investigate the influence of crushing on the pharmacokinetics of the elbasvir/grazoprevir fixed-dose combination tablet. Methods We conducted an open-label, two-period, randomized, cross-over, Phase I, single-dose trial in 11 healthy adult volunteers. Subjects randomly received whole-tablet elbasvir/grazoprevir or crushed and suspended elbasvir/grazoprevir in a fasted state. Pharmacokinetic similarity criteria (90% CIs lie within 70%–143% acceptance range) were used for AUC0–∞ and AUC0–72. Results Mean plasma concentration–time curves of elbasvir and grazoprevir showed similar pharmacokinetic profiles. The primary pharmacokinetic parameters AUC0–∞ and AUC0–72 of elbasvir and grazoprevir after intake of a crushed tablet were on average 12%–16% higher compared with the whole tablet, but 90% CIs were all within the predefined boundaries of pharmacokinetic similarity. Crushing leads to a higher Cmax of grazoprevir (42%); no significant difference was found between treatments with regard to the Cmax of elbasvir. No serious adverse events were reported during the trial. Conclusions Pharmacokinetic similarity could be demonstrated for a crushed and suspended tablet compared with a whole tablet, without impacting drug safety or efficacy. Crushed and suspended administration of elbasvir/grazoprevir can be used in patients with swallowing disorders.