Transplantation has become the therapy of choice for patients with organ failure. However, the low rate of consent by families of donor-eligible patients is a major limiting factor in the success of organ transplantation. To explore factors associated with the decision to donate among families of potential solid organ donors. Data collection via chart reviews, telephone interviews with health care practitioners (HCPs) or organ procurement organization (OPO) staff, and face-to-face interviews with family for all donor-eligible deaths at 9 trauma hospitals in southwestern Pennsylvania and northeastern Ohio from 1994 to 1999. Family members, HCPs, and OPO staff involved in the donation decision for 420 donor-eligible patients. Factors associated with family decision to donate or not donate organs for transplantation. A total of 238 of the 420 cases led to organ donation; 182 did not. Univariate analysis revealed numerous factors associated with the donation decision. Multivariable analysis of associated variables revealed that family and patient sociodemographics (ethnicity, patient's age and cause of death) and prior knowledge of the patients' wishes were significantly associated with willingness to donate (adjusted odds ratio [OR], 7.68; 95% confidence interval [CI], 6.55-9.01). Families who discussed more topics and had more conversations about organ donation were more likely to donate (adjusted OR, 5.22; 95% CI, 4.32-6.30), as were families with more contact with OPO staff (adjusted OR, 3.08; 95% CI, 2.63-3.60) and those who experienced an optimal request pattern (adjusted OR, 2.96; 95% CI, 2.58-3.40). Socioemotional and communication variables acted as intervening variables. Public education is needed to modify attitudes about organ donation prior to a donation opportunity. Specific steps can be taken by HCPs and OPO staff to maximize the opportunity to persuade families to donate their relatives' organs.