Background Identification of modifiable psychosocial characteristics related to survival of heart transplant (HTx) candidates is needed to prevent clinical deterioration and improve prognosis. Methods A multi-site, prospective study was conducted with 318 HTx candidates (18% female, 82% male; 53 ± 11 years of age) newly listed at 17 hospitals in Germany and Austria. Baseline demographic and psychosocial characteristics were assessed by questionnaires. Indicators of disease severity (Heart Failure Survival Score, creatinine, cardiac index) and 12-month outcomes (death, high-urgency HTx, elective HTx, de-listing due to deterioration or improvement) were provided by Eurotransplant. Results By 12 months, 33 patients died, 83 received an urgent HTx, 30 underwent an elective HTx, and 9 were de-listed due to clinical deterioration and 17 due to improvement. All measures of disease severity predicted outcomes. Controlling for disease severity, the number of social contacts contributed significantly to outcomes, favoring those who improved. Comparing socially isolated patients (<4 social contacts/month) who also had depression scores in the clinical range (high psychosocial risk group; n = 37) to those with >10 social contacts/month without depression (low psychosocial risk group; n = 47) revealed significant differences in the distribution of outcome frequencies (chi-square = 11.2, df = 4, p < 0.04). The high psychosocial risk group was more likely to have died/deteriorated and less likely to have improved than the low psychosocial risk group. Conclusions Regardless of disease severity, socially isolated HTx candidates who are also depressed may be at increased risk for clinical deterioration and mortality, indicating a need for psychosocial intervention.