**Background:** As COVID-19 vaccination campaigns expand to adolescents globally, understanding vaccine hesitancy in this population is critical, particularly in sub-Saharan Africa where adolescents comprise 23% of the population. While multiple studies have examined adult vaccine hesitancy in low- and middle-income countries, no study had specifically assessed hesitancy among adolescents across diverse sub-Saharan African settings. This study aimed to fill that gap.
**Methods:** This cross-sectional, multi-country survey was conducted between July and December 2021 using computer-assisted telephone interviewing. Nine areas across five countries were included: Nouna (rural) and Ouagadougou (urban) in Burkina Faso; Kersa (rural) and Addis Ababa (urban) in Ethiopia; Kintampo (rural) in Ghana; Ibadan (rural subarea) and Lagos (urban) in Nigeria; and Dodoma (rural) and Dar es Salaam (urban) in Tanzania. Households were sampled from existing Health and Demographic Surveillance Systems or national surveys, with approximately 300 adolescents per area (total n=2,662). Adolescents aged 10–19 years were interviewed after obtaining parental consent and adolescent assent. The survey assessed sociodemographics, awareness and perceptions of COVID-19 vaccines, willingness to vaccinate, trusted information sources, and potential determinants of hesitancy. Vaccine hesitancy was defined as responding "definitely not" or "maybe/unsure/undecided" to getting vaccinated if a vaccine were available. Log-binomial models estimated adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs), controlling for age, sex, country, and rural residence.
**Key Results:** COVID-19 vaccine hesitancy varied dramatically across sites: 14% in Kersa (Ethiopia), 23% in Ibadan (Nigeria), 31% in Nouna (Burkina Faso), 32% in Ouagadougou (Burkina Faso), 37% in Addis Ababa (Ethiopia), 48% in Kintampo (Ghana), 65% in Lagos (Nigeria), 76% in Dar es Salaam (Tanzania), and 88% in Dodoma (Tanzania). Among hesitant adolescents, the leading reasons were perceived low necessity (47%), concerns about vaccine safety (45%), and concerns about effectiveness (11%). Among those willing to vaccinate, keeping self and family safe was the most common reason (94%), followed by parental/family will (72%) and doctor's suggestion (63%). Perceived lack of safety was strongly associated with hesitancy: compared to those perceiving vaccines as "very safe," adolescents perceiving vaccines as "not safe at all" had 3.52 times the prevalence of hesitancy (aPR 3.52; 95% CI: 3.00, 4.13). Similarly, perceived lack of effectiveness showed a strong gradient: those perceiving vaccines as "not effective at all" had 3.46 times the prevalence of hesitancy (aPR 3.46; 95% CI: 2.97, 4.03) versus those perceiving them as "very effective." Boys had slightly lower hesitancy than girls (aPR 0.92; 95% CI: 0.86, 0.99). Compared to Burkina Faso, hesitancy was similar in Ethiopia (aPR 0.92; 95% CI: 0.75, 1.13), but significantly higher in Ghana (aPR 1.59; 95% CI: 1.32, 1.92), Nigeria (aPR 1.51; 95% CI: 1.29, 1.78), and Tanzania (aPR 2.51; 95% CI: 2.18, 2.89). The most trusted information sources were television/radio/newspaper (85%), medical professionals (83%), and government communications (73%). Healthcare workers (60%), parents/family (58%), and schoolteachers (46%) had the greatest influence on vaccine willingness.
**Clinical Implications:** The alarmingly high prevalence of COVID-19 vaccine hesitancy among sub-Saharan African adolescents—particularly in Tanzania, where 88% in Dodoma and 76% in Dar es Salaam were hesitant—poses a major barrier to achieving herd immunity and controlling the pandemic in the region. Vaccination campaigns must directly address misconceptions about vaccine safety and effectiveness, as these were the strongest modifiable predictors of hesitancy. Leveraging trusted messengers—healthcare workers, parents, teachers, and religious leaders—will be essential. The finding that over 30% of adolescents would be more willing to receive a vaccine developed or tested in Africa underscores the importance of local vaccine development and technology transfer. Special attention should be directed toward adolescent girls, who showed higher hesitancy than boys. Limitations include non-probabilistic sampling within each area and potential underrepresentation of adolescents from households without phone access, which may affect generalizability.