This study used a cross-sectional online survey design with a self-developed questionnaire to assess vaccine confidence, hesitancy and factors influencing vaccine acceptance among 314 adult Nigerians. The questionnaire covered sociodemographic characteristics, health and lifestyle factors, vaccine knowledge and experiences. The data analysis included descriptive statistics and odds ratio calculations with 95% confidence intervals. Most respondents were young adults, with high rates of childhood vaccination completion and COVID-19 vaccine uptake. Trust in healthcare professionals and belief in vaccine effectiveness were strongly associated with higher vaccine acceptance, whereas females, individuals with previous unpleasant side effects, and those who knew someone who refused vaccination showed greater hesitancy. Open-ended responses revealed misinformation, religious or personal beliefs and competing priorities as additional reasons for vaccine refusal. Overall, vaccine acceptance was relatively high, but persistent concerns about safety and trust emphasize the need for transparent communication and stronger pharmacist involvement in vaccine education and community engagement.