Community-acquired pneumonia (CAP) can be caused by a variety of microorganisms but is most frequently associated with Streptococcus pneumoniae and gram-negative bacteria like Haemophilus influenzae. Encapsulated bacteria are able to escape phagocytosis, unless they are bound by immunoglobulin G2 subclass antibodies. These antibodies interact with Fcgamma receptor IIa (Fcgamma-RIIa), thereby facilitating opsonophagocytosis of the encapsulated bacteria. We studied the relationship between the Fcgamma-RIIa-R/H131 polymorphism and the clinical course of CAP and pathogen-specific susceptibility. Regarding methodology, the Fcgamma-RIIa genotype R/H131 was determined in 200 patients with CAP and in 313 healthy controls and was correlated with the clinical course, laboratory parameters, and causative microorganism. The Fcgamma-RIIa-R/R131 genotype was found more frequently in patients with severe sepsis (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.30 to 5.00; P < 0.01). The majority of patients in this group suffered from invasive pneumococcal disease. The duration of hospital stay was longer for patients with the Fcgamma-RIIa-R/R131 genotype. Fcgamma-RIIa genotypes were not associated with an increased risk of CAP in general; however, the Fcgamma-RIIa-R/R131 genotype was found more frequently in patients with CAP caused by H. influenzae than in controls (OR, 3.03; CI, 1.04 to 9.09; P < 0.05). In conclusion, the Fcgamma-RIIa-R/R131 genotype is associated with severity of CAP and is more frequent in CAP caused by H. influenzae.