Background <p>Typhoid poses a significant challenge in India, which has one of the highest burdens of the disease globally, making the implementation of cost-effective vaccination strategies essential. The success of typhoid vaccination, whether through clinical trials or large-scale public health programmes, depends on community acceptance. In the post-COVID-19 period, vaccine hesitancy and scepticism have emerged as key challenges to both vaccine trials and mass vaccination efforts. This study examines the barriers to and motivations for vaccine uptake during a mass vaccination campaign.</p> Methods <p>We conducted 15 focus group discussions (FGDs) and five in-depth interviews (IDIs) with participants and guardians from a cluster-randomised typhoid vaccine trial in Vellore, India. Data collection occurred two months after the vaccination campaign in purposively selected low- and high-coverage areas. FGD categories were determined a priori based on age, gender, and vaccination status, while IDIs were conducted when FGDs were not feasible. Data were collected until thematic saturation was achieved. The interviews were audio-recorded, transcribed, and analysed using thematic analysis.</p> Results <p>Vaccination decisions were shaped by a combination of safety concerns, risk perceptions, and social influences. Key barriers included fears of long- and short-term adverse events, low perceived disease risk and consequently a reduced perceived need for vaccination, shifting attitudes toward new and adult vaccination following COVID-19, sociocultural beliefs, objections from household decision-makers, perceived lack of visible government endorsement and participation, and trust in alternative systems of medicine. The motivators included increased disease salience after the COVID-19 pandemic, increased perceived disease risk, positive influence from family members and peers, and trust in healthcare providers and professional recommendations. Study-related benefits, such as access to vaccines, follow-up, and free vaccination, operated bidirectionally, motivating many participants while raising concerns about vaccine quality among a few.</p> Conclusion <p>In the post–COVID-19 era, vaccine availability alone does not ensure uptake. Vaccination programmes should actively engage household decision-makers, leverage trusted healthcare providers, address safety concerns and misconceptions surrounding new and free vaccines, and strengthen community trust alongside logistical planning.</p>