Seasonal influenza infections cause significant morbidity and mortality, with ~500,000 deaths annually. Current vaccination regimens are the best method to combat annual influenza disease, although efficacy varies across years and can be low in high-risk groups. Haematopoietic stem cell transplant (HSCT) recipients are at high risk of severe influenza infection and show impaired immune responses towards inactivated influenza vaccine (IIV), especially within six months post-HSCT. We investigated humoral immunity to the trivalent IIV in a cohort of HSCT recipients (n=18) in comparison to healthy controls (n=14). IIV significantly increased hemagglutination inhibition (HAI) titres in HSCT recipients, similar to healthy controls. A systems serology approach revealed increased levels of IgG1 and IgG3 antibodies towards influenza-specific haemagglutinin (HA) head, but not to neuraminidase, nucleoprotein or HA stem. IIV also increased the frequency of total, IgG class-switched and activated-memory (CD21loCD27+) influenza-specific B-cells, determined by recombinant HA-probes and flow cytometry. For those HSCT recipients who did not respond to the first dose, the second IIV dose did not improve humoral responses, although some donors reached a seroprotective HAI titre (≥40). Strikingly, selected HSCT recipients had profoundly higher antibody responses towards the A/H3N2 vaccine strain compared to healthy controls, and even showed cross-reactivity to antigenically-drifted A/H3N2 strains. Such superior responses were associated with a greater time-interval after HSCT and multivariant analyses revealed the importance of pre-existing immune memory. Overall, our study demonstrated efficient but variable immune responses to IIV across HSCT recipients. The findings provide insights into influenza vaccination strategies targeted to immunocompromised high-risk groups and the efficacy of two IIV doses.