Objective: Susceptibility to periodontal disease (PD) is partially genetically determined and HLA genes are candidates for playing a role in the genetic background of susceptibility as their products are essential in immune response against periopathogenic bacteria. The literature relating to HLA and PD identifies conflicting ranges of possible HLA associations as different ethnic origin and diagnoses have been examined in several studies. Therefore, the aim of the study was to estimate the overall associations between HLA phenotypes among Caucasians and to establish the odds ratio conferred by HLA phenotypes by meta-analysis. Methods: Literature search was done for publications reporting on the relation between PD and HLA class I and II phenotypes. Case-control studies with clearly described diagnostic criteria for patients and controls of Caucasian origin were considered for combined analyses. Periodontal diagnoses were adapted to the latest nomenclature of the AAP. Odds ratios were calculated using both fixed-effects and random-effects-model when appropriate. Results: The search yielded a list of 18 Caucasian case-control studies, of which 11 were included for meta-analysis. In patients with aggressive periodontitis (AP) positive associations to HLA-A9 (OR = 2.18) and -B15 (OR = 1.81) and a negative association to HLA-B5 (OR = 0.50) were identified. In patients with chronic periodontitis (CP) no positive HLA association was found. For both CP and AP there was a clear evidence for a negative association to HLA-A2 (CP: OR = 0.59; AP: OR = 0.69). Conclusion: The results suggest HLA-A2 to be a protective factor for CP and AP among Caucasians, whereas HLA-A9 and -B15 might contribute genetic background susceptibility factors for aggressive periodontitis. Further subgroup and combination analyses of these HLA markers as well as their associations to peptides of periodontopathic bacteria may elucidate how these markers confer susceptibility or resistance to AP or CP. Keywords: periodontitis, HLA, MHC