Background Patterns of symptom frequency and distress have not been examined long-term after heart transplantation, nor have predictors of long-term symptom frequency and distress. This report identified the most commonly reported and distressful symptoms long-term after transplantation, described patterns of symptom frequency and distress over time, and examined predictors of symptom frequency and distress at 5 and 10 years after heart transplantation. Methods The sample included 555 participants from a prospective, multisite, longitudinal study of quality of life outcomes. Patients were 78% male, 88% white, 79% married, and mean age of 54 years at time of heart transplantation. Data were collected using patient self-report and medical records review. Statistical analyses included descriptive statistics, Pearson correlations, t-tests, and generalized linear models. Results Significant predictors of lower symptom frequency after heart transplantation were not having psychological problems and not having cardiac allograft vasculopathy at 5 years, and not having psychological problems and not having infection at 10 years. Significant predictors of less symptom distress were having more than a high school education, having no psychological problems, and having gout at 5 years, and being married at 10 years. Conclusions Symptom frequency is low and symptom distress is moderate long-term after heart transplantation. Significant relationships exist between both demographic and clinical variables and symptom frequency and distress. Identification of the most common and bothersome symptoms after heart transplantation provides clinicians with important information from which to develop a plan of care.