OBJECTIVE: To evaluate the effect of the introduction of the Haemophilus influenzae B (Hib) vaccine (introduced first in 1985, then extended in 1990 to children at least 2 months of age) on the epidemiologic features of periorbital and orbital cellulitis. DESIGN: Retrospective, comparative case series. PARTICIPANTS: Three hundred fifteen pediatric inpatients. METHODS: Children at Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary with discharge diagnosis of periorbital or orbital cellulitis from 1980 through 1998 were reviewed. MAIN OUTCOME MEASURES: Case rate, culture-positive isolates, and associated conditions. RESULTS: A total of 297 cases of periorbital cellulitis and 18 cases of orbital cellulitis were reviewed. Before 1990, there were 27 cases of Hib-related cellulitis (11.7% of total in that period), whereas after 1990, there were only three (3.5% of total; P = 0.028). The number of cases per year was significantly lower after 1990 (21.2 +/- 10.4 vs. 8.7 +/- 3.9; P = 0.008), as were the number of positive culture isolates (for any organism) after 1990 (76 [33. 0%] vs. 9 [10.6%]; P < 0.001). The medical conditions most commonly associated with periorbital cellulitis were sinusitis (44 [14.5%]) and upper respiratory infections (73 [26.6%]). All cases of orbital cellulitis were associated with sinusitis. CONCLUSIONS: The introduction of the Hib vaccine coincided with a sharp decline not only in the number of periorbital and orbital cellulitis cases related to H. influenzae, but also in the annual case rate. These data are consistent with a facilitative role for H. influenzae in the development of cellulitis secondary to other pathogens. They also may support restriction of the spectrum of antibiotics used to manage these conditions.