To evaluate risk factors for human infection with influenza A subtype H5N1, we performed a matched case-control study in Vietnam. We enrolled 28 case-patients who had laboratory-confirmed H5N1 infection during 2004 and 106 age-, sex-, and location-matched control-respondents. Data were analyzed by matched-pair analysis and multivariate conditional logistic regression. Factors that were independently associated with H5N1 infection were preparing sick or dead poultry for consumption <7 days before illness onset (matched odds ratio [OR] 8.99, 95% confidence interval [CI] 0.98–81.99, p = 0.05), having sick or dead poultry in the household <7 days before illness onset (matched OR 4.94, 95% CI 1.21–20.20, p = 0.03), and lack of an indoor water source (matched OR 6.46, 95% CI 1.20–34.81, p = 0.03). Factors not significantly associated with infection were raising healthy poultry, preparing healthy poultry for consumption, and exposure to persons with an acute respiratory illness.