We analysed Australian Immunisation Register (AIR) data as at 3 April 2022 for children, adolescents and adults for the calendar year 2021, with data on trends from previous years also presented. 'Fully vaccinated' coverage in Australian children in 2021 was 0.6-0.8 of a percentage point lower than in 2020 at the 12-month (94.2%) and 60-month (94.0%) age assessment milestones, but stable at the 24-month milestone (92.1%). Due to the lag time involved in assessment at milestone ages, 'fully vaccinated' coverage figures for 2020 and 2021 predominantly reflect vaccinations due in 2019 and 2020, respectively, and hence show a small impact on childhood coverage in the first year of the coronavirus disease 2019 (COVID-19) pandemic. 'Fully vaccinated' coverage in Aboriginal and Torres Strait Islander (hereafter respectfully referred to as Indigenous) children was 0.7-1.5 percentage points lower in 2021 than 2020 at the 12-month (91.6%), 24-month (90.1%) and 60-month (96.3%) milestones, although 2.3 percentage points higher than children overall at 60 months. Influenza vaccination coverage in children aged 6-59 months was approximately 20 percentage points lower in 2021 than 2020, both for children overall (26.5%) and for Indigenous children (22.5%). 'On time' vaccination (within 30 days of the recommended age) was up to two percentage points lower in 2021 than 2020 for vaccines due at 4 and 6 months of age, suggesting possible pandemic impacts, but was similar or higher for vaccines due at 12 months of age. While on-time vaccination in Indigenous children has improved progressively since 2012, it remained 6-13 percentage points lower than in children overall in 2021. 'Fully vaccinated' coverage at the earlier milestones (3 months after due date of last scheduled vaccine) of 9, 15, 21 and 51 months was 1.5-2.8 percentage points lower for children living in the least advantaged residential area quintile than the most advantaged, a similar disparity as in 2020. Coverage at the earlier milestones was 2.3-10.0 percentage points lower for Indigenous children living in remote areas than in major cities and regional areas, with disparity at 21 months of age 2.1-2.2 percentage points higher in 2021 than in 2020, and 1.2-2.1 percentage points higher at 51 months. In 2021, a total of 80.3% of girls and 77.2% of boys (and 73.3% and 66.2% of Indigenous girls and boys) had completed the human papillomavirus (HPV) vaccination schedule by 15 years of age, 0.2-0.4 of a percentage point lower than 2020 (1.7-1.8 percentage points for Indigenous), reflecting vaccinations due in school programs prior to the pandemic with possible pandemic impact on catch-up vaccination. However, the proportion of adolescents completing the two-dose HPV vaccination schedule within a calendar year was 15.3 percentage points lower in 2021 than 2020 and 26.9 percentage points lower than in 2019, likely due to pandemic-related disruption to school-based programs. Additionally, 87.3% of adolescents (83.8% for Indigenous) had received the recommended booster dose of diphtheria-tetanus-acellular pertussis (dTpa) vaccine by 15 years, and 76.1% (66.7% for Indigenous) the recommended meningococcal ACWY vaccine dose by 17 years of age. Zoster vaccine coverage in 2021 remained relatively low, at just over 30%, in adults aged 70 years, but increased to 47% in those aged 71-79 years, reflecting ongoing catch-up vaccination. Coverage of 13vPCV was low in 2021, reaching 17.2% in adults aged 70 years and 20.1% in those aged 71-79 years. Influenza vaccination coverage in adults in 2021 was progressively higher with increasing age, reaching 62.1% in the 65-74 years age group (64.6% in Indigenous) and 68.5% in the 75+ years age group (67.7% in Indigenous). Influenza vaccine coverage for other National Immunisation Program (NIP)-eligible Indigenous adult age groups was only 22.0% for those aged 20-49 years, and 43.5% for those aged 50-64 years. By the end of 2021, a total of 91.6% of people in Australia aged 16+ years had received a second dose of a COVID-19 vaccine (71.8% for Indigenous), with over 99% of those aged 70+ years having received a second dose. Vaccination coverage in children and adolescents remained relatively high in 2021, although with some evidence of COVID-19 pandemic impacts, particularly on receipt of two doses of HPV vaccine within the same calendar year. It will be important to ensure catch-up vaccination in children and adolescents occurs. A strengthened focus on adult vaccination is needed, as coverage remained suboptimal in 2021. The impact of mandatory reporting of all NIP vaccinations from mid-2021, on completeness of AIR data, has not yet been formally evaluated.