BACKGROUND: Vaccination has been shown to attenuate the risk of postacute sequelae following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, no prior population-based studies have evaluated if updated bivalent boosters reduce risk of postacute sequelae following Omicron variant infection, versus ancestral vaccines. METHODS: National databases were utilized to construct a population-based cohort of adult individuals infected during Omicron-predominant transmission. Risk and excess burden (EB) of prespecified multiorgan new-incident diagnoses at 31-365 days post-SARS-CoV-2 infection were compared between individuals who received prior bivalent boosters and those boosted with ancestral messenger RNA (mRNA) vaccines, using competing-risks regression. RESULTS: A total of 1 080 348 vaccine-breakthrough infections after an ancestral mRNA booster were contrasted against 9824 vaccine-breakthrough infections following a bivalent mRNA booster. There was an estimated 37.8% (hazard ratio [HR], 0.62 [95 confidence interval {CI}, .53-.73]) decrease in risk and lower overall EB per 1000 (-28.73 [95% CI, -40.47 to -16.99]) of any postacute sequelae, as well as a 39.9% (HR, 0.62 [95% CI, .52-.73]) decrease in risk and lower EB (-22.95 [95% CI, -32.71 to -13.19]) of any postacute neurological sequelae, among individuals who received prior bivalent boosters, versus those boosted with ancestral mRNA vaccines. Specifically, there was reduced risk of thrombotic disorders (HR, 0.54 [95% CI, .29-.99]), episodic neurological disorders (HR, 0.55 [95% CI, .43-.72]), movement disorders (HR, 0.57 [95% CI, .47-.70]), and autoimmune vasculitis (HR, 0.54 [95% CI, .29-.99]) 31-365 days postinfection among those who received prior bivalent boosters, versus those boosted with ancestral mRNA vaccines. CONCLUSIONS: Boosting with updated bivalent mRNA vaccines was associated with greater attenuation of risk for postacute sequelae following Omicron variant infection, compared with ancestral mRNA boosters.