Background From clinical experience, kinesiophobia represents a barrier to being physically active after a heart transplantation (HTx), but studies in this field are lacking. Identifying the factors associated with kinesiophobia is essential to determine preventive interventions to avoid negative consequences for health. Aims To study the influence of disability, physical, and behavioural variables on kinesiophobia in patients with an HTx. Methods A total of 117 patients with an HTx [51 women; mean age 56 (SD 12.1) years] were recruited at an outpatient clinic. These patients were asked to fill in questionnaires measuring kinesiophobia, self-reported physical activity (PA), exercise self-efficacy, motivation for PA, and disability. A multiple regression analysis was conducted to examine the statistical prediction of kinesiophobia as a dependent variable, with the questionnaires, gender and education as independent variables. Results The independent variables explained 70% of the variance in kinesiophobia. The prediction model was significant (F = 32.1, P < 0.001). The time from transplantation (standardised coefficient, beta; -0.17), the total exercise self-efficacy (-0.16), extrinsic motivation (-0.23), and the disability total score (0.63) were significant predictors of kinesiophobia, while the independent variables of gender, education, intrinsic motivation, and the PA total score were not significant. Conclusions This study highlights that a short time from transplantation, low self-efficacy, low extrinsic motivation, and a high level of disability explained high levels of kinesiophobia in patients after an HTx. These results suggest that an increased awareness of the biopsychosocial health perspective is essential in order to maximising patient outcomes after an HTx.