•Mercerization successfully controlled the dimensions of native BNC conduits.•Superior mechanical properties of BNC conduits were achieved via mercerization.•Mercerized BNC (MBNC) conduits exhibited nice hemocompatibility in absence of bioactive compounds.•MBNC conduits satisfied a long-term patency over 16 weeks in a rat abdominal aorta model. Bacterial nanocellulose (BNC) is a natural polysaccharide synthesized principally by Komagataeibatacter xylinus which can be formed into tubes and other shapes through the use of special bioreactors. Although tubular BNC has considerable potential as a small-caliber vascular graft (<6 mm), its poor mechanical properties in its hydrogel form, lack of compliance, and its thick walls that do not match natural vessels limit their potential clinical use and long-term patency rate after implantation. Mercerization is an approach in which an alkaline treatment changes the chemistry of BNC products. Following mercerization, tubular BNC grafts exhibited greater mechanical strength combined with thinner walls. Volumetric reduction of the tubular BNC was effective (by nearly 90%) when using a NaOH concentration greater than 10% (w/v), which caused fewer platelets to adhere to the luminal surface. Mercerized tubular BNC (MBNC) promoted the proliferation of endothelial cells in vitro. The MBNC obtained using 20% NaOH was selected for transplantation within a rat abdominal aorta model. Normal blood flow was observed for 16 weeks, indicating that the MBNC conduit maintained long-term patency. The results indicate that mercerization can control the size of tubular BNC and thus the MBNC conduit is a promising candidate for blood vessel replacement.