Abstract Background Invasive meningococcal disease (IMD) is most common in the first year of life. We hypothesized that preterm infants may have a higher risk of IMD and more severe disease than term infants. We compared the incidence, demographics, clinical presentation, and outcomes of IMD in preterm compared with term infants during the first 5 years after implementation of a national meningococcal group B vaccine (4CMenB) for infants in England. Methods The UK Health Security Agency conducts enhanced national IMD surveillance with detailed follow-up of all confirmed cases in England. Infants aged <1 year (uncorrected for gestational age) with IMD confirmed between 1 September 2015 and 31 August 2020 were included. Results There were 393 infant IMD cases (incidence, 12.4/100 000 live births). Among 363 (92.4%) of the infants with known gestational age, the IMD incidence was higher in preterm (<37 weeks’ gestation) than in term infants (18.3/100 000 vs 10.9/100 000; incidence rate ratio [IRR], 1.68 [95% confidence interval, 1.23–2.29]; P = .001). The IMD incidence was highest in those born at <32 weeks’ gestation (32.9/100 000; incidence rate ratio for <32 weeks’ gestation vs term, 3.01 [95% confidence interval, 1.73–5.24]; P ≤ .001). There were no differences in demographics, clinical presentation, rate of intensive care admission, or case-fatality rate, but preterm infants were more likely than term infants to have ≥1 reported sequela (14 of 39 [35.9%] vs 51 of 268 [19.0%]; P = .02). Conclusions Preterm infants had a higher incidence of IMD than term infants and the IMD incidence was highest in infants born at <32 weeks’ gestation. Preterm infants also had a higher risk of IMD sequelae.