On April 26, 2015, a case of meningococcal disease in a woman aged 75 years was reported to the Colorado Department of Public Health and Environment (CDPHE). As part of routine public health investigation and control activities, all seven family contacts of the patient were advised to receive appropriate postexposure prophylaxis (PEP) to eradicate nasopharyngeal carriage of meningococci and prevent secondary disease (1), although it is not known whether the family contacts complied with PEP recommendations. Fifteen months later, on June 6, 2016, CDPHE was notified that the grandchild of the first patient, a male infant aged 3 months who lived with the first patient, also had meningococcal disease. The infant's immediate family members (parents and one sibling) were among family contacts for whom PEP was recommended in 2015. Neisseria meningitidis isolates from both patients were found to be serogroup C at the CDPHE laboratory. Whole genome sequence (WGS) analysis at CDC found that both isolates had the same sequence type, indicating close genetic relatedness. These cases represent a possible instance of meningococcal disease transmission within a family, despite appropriate PEP recommendations and with a long interval between cases.