This study was carried out in order to assess the validity of the pure cross-sectional study in the ascertainment of nosocomial infection risk-factors. The results yielded by two designs (crosssectional and case-control) are compared. A cross-sectional design was performed in a tertiary hospital. 592 patients were studied, 38 of whom were nosocomially infected. The clinical information on all the patients included in this design was reviewed after hospital discharge. A matched case-control study was nested in the population cross-sectionally surveyed. 66 cases (28 additional patients developed a hospital infection) and 132 controls were selected. Odds ratios (ORs) for the risk factors analyzed by both designs were compared. There were no significant differences between the estimates yielded by both designs; however, a trend of lower OR estimates for the cross-sectional study was seen, which may be important for risk factors not strongly related to (low relative risk) nosocomial infection. Several factors which might account for the results observed (random error, bias introduced by matching) are discussed. It is suggested that pure cross-sectional designs for the study of risk factors of nosocomial infection may introduce a negative (toward-thenull) bias.