BACKGROUND:: Human immunodeficiency virus (HIV)-infected children are at increased risk of meningococcal infection and poor response to quadrivalent meningococcal conjugate vaccine (MCV4), but MCV4 has not been studied in preadolescent HIV-infected children. METHODS:: The P1065 trial enrolled 2- to 10-year-old HIV-infected children with CD4 >/=25% to receive MCV4 at entry and at week 24. Rates of response (>/=4-fold increase in rabbit serum bactericidal antibody) against each meningococcal serogroup (A, C, Y, W-135), geometric mean titers, and rates of seroprotection (rabbit serum bactericidal antibody titer >/=1:128) were determined from sera obtained at entry and weeks 4, 24, 28, and 72. Adverse events were assessed for 6 weeks after each MCV4 dose. RESULTS:: At entry, 47% of the 59 participants were male, 56% black, 31% Latino, median age was 6 years, 88% were receiving antiretroviral therapy, and 75% had viral load <400 copies/mL. There were no serious adverse events within 6 weeks after MCV4 doses; all vaccination reactions were mild. Response after a single MCV4 dose was high to serogroup A (92%) and W-135 (98%); responses improved after a second dose for serogroup C (43%-80%) (P < 0.0001) and Y (76%-84%) (P = 0.38). By week 72, seroprotection rates were 93%, 91%, 78%, and 46% for serogroups W-135, Y, A, and C, respectively. CONCLUSIONS:: Two doses of MCV4 were safe and immunogenic in 2- to 10-year-old HIV-infected children. The second dose increased the proportion of children who made a response to serogroup C. Seroprotection waned substantially for serogroups A and C within 1 year of last MCV4 dose.