We estimated the relative protective efficacy of Haemophilus influenzae type b polysaccharide (PRP) vaccine and PRP-diphtheria toxoid-conjugate (PRP-D) vaccine using data from reports of cases of invasive Haemophilus disease occurring in vaccinated children submitted to the Food and Drug Administration, Rockville, Md, and Washington University, St Louis, Mo. During the first 13 months following licensure of each of the vaccines, there were 127 cases reported in recipients of PRP vaccine vs 17 cases in recipients of PRP-D vaccine. The total number of reported cases for each vaccine is not necessarily comparable, since the extent of vaccine use in the population and the extent of reporting of cases may have been different during the two periods. However, the proportion of reported cases occurring equal to or 14 days or more after vaccination (a period considered sufficient to develop immunity) was significantly greater for PRP vaccine (106 [83%] of 127 cases) compared with PRP-D vaccine (7 [41%] of 17 cases). Based on the ratio of late-onset to early-onset cases observed for PRP vaccine, we would have expected 50 late-onset cases after PRP-D vaccination. Since only 7 late-onset PRP-D vaccine failures were reported (86% fewer than expected), the data suggest that PRP-D vaccine was more effective in preventing disease 14 days or more after vaccination than was PRP vaccine.