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Following the results of the ENSEMBLE 2 study, which demonstrated improved vaccine efficacy of a two-dose regimen of Ad26.COV.2 vaccine given 2 months apart, we expanded the Sisonke study which had provided single dose Ad26.COV.2 vaccine to almost 500 000 health care workers (HCW) in South Africa to include a booster dose of the Ad26.COV.2. Sisonke 2 enrolled 227 310 HCW from the 8 November to the 17 December 2021. Enrolment commenced before the onset of the Omicron driven fourth wave in South Africa affording us an opportunity to evaluate early VE in preventing hospital admissions of a homologous boost of the Ad26.COV.2 vaccine given 6-9 months after the initial vaccination in HCW. We estimated vaccine effectiveness (VE) of the Ad26.COV2.S vaccine booster in 69 092 HCW as compared to unvaccinated individuals enrolled in the same managed care organization using a test negative design. We compared VE against COVID19 admission for omicron during the period 15 November to 20 December 2021. After adjusting for confounders, we observed that VE for hospitalisation increased over time since booster dose, from 63% (95%CI 31-81%); to 84% (95% CI 67-92%) and then 85% (95% CI: 54-95%), 0-13 days, 14-27 days, and 1-2 months post-boost. We provide the first evidence of the effectiveness of a homologous Ad26.COV.2 vaccine boost given 6-9 months after the initial single vaccination series during a period of omicron variant circulation. This data is important given the increased reliance on the Ad26.COV.2 vaccine in Africa.