Influenza vaccination can be less effective in patients treated with immunosuppressive therapy. However, little is known about the effects of ustekinumab; an anti-IL-12/23 agent used to treat Crohn’s disease (CD), on vaccination response. In this prospective study, we assessed immune responses to seasonal influenza vaccination in CD patients treated with ustekinumab compared to CD patients treated with anti-TNFα therapy (adalimumab) and healthy controls. Humoral responses were assessed with hemagglutinin inhibition (HI) assays. Influenza-specific total CD3+, CD3+CD4+, and CD3+CD8+ T-cell responses were measured with flow cytometry. Fifteen patients treated with ustekinumab; 12 with adalimumab and 20 healthy controls were vaccinated for seasonal influenza in September 2018. Seroprotection rates against all vaccine strains in the ustekinumab group were high and comparable to healthy controls. Seroconversion rates were comparable, and for A/H3N2 highest in the ustekinumab group. HI titers were significantly higher in the ustekinumab group and healthy controls than in the adalimumab group for the B/Victoria strain. Post-vaccination T-cell responses in the ustekinumab group were similar to healthy controls. One-month post-vaccination proliferation of CD3+CD8+ T-cells was highest in the ustekinumab group. In conclusion, ustekinumab does not impair immune responses to inactivated influenza vaccination. Therefore, CD patients treated with ustekinumab can be effectively vaccinated for seasonal influenza.