Purpose Adult heart transplant (HTx) recipients receive steroids early post-transplant to minimize the risk of rejection and mortality. There are however no specific, evidence-based recommendations for the optimal steroid regimen (i.e. treatment dose, and duration of therapy) post-HTx. This study aims to determine if the steroid dose used post-HTx is independently associated with increased mortality. Methods We identified adult (≥18 years) HTx recipients transplanted between 2000-2020 at the Toronto General Hospital (Toronto, Canada) and Rigshospitalet (Copenhagen, Denmark) who survived the first week post-HTx. We collected daily use of steroids and expressed doses in daily weight adjusted prednisone-equivalent dose in mg/kg until death or date of last follow-up. We conducted multivariable Cox regression models, treating prednisone dose as a time-dependent covariate to evaluate the independent association with all-cause mortality, adjusted for recipient and donor age, recipient BMI, recipient-donor sex mismatch, previous sternotomy, ischemic time and use of short or long term mechanical circulatory support pre-HTx. Results We identified 545 HTx recipients with 7,138 documented prednisone doses post-HTx. Of these HTx recipients, 102 died during a median follow-up of 6.6 years. By multivariable analysis, a 0.1 mg/kg increase in daily prednisone dose was associated with a 1% increase in all-cause mortality (1.013 (95% CI 1.004 - 1.022)). The effect of steroids was constant over time. The absolute mortality in patients not using prednisone at 6-months was 16% at 5-years and 27% at 10-years. In patients on 0.1 mg/kg at 6-months, their absolute risk increases to 17% at 5-years and 28% at 10-years. Conclusion Among adult HTx recipients who survive the first week post-HTx, an increase in prednisone dose is associated with increased mortality. The absolute effect on mortality, however, is clinically insignificant for commonly used long term doses of steroids, such as 0.1 mg per kg of body mass, daily. These results suggest that the early withdrawal of steroids has minimal impact on the risk of post-transplant mortality. The impact on specific post-transplant morbidities remains to be estimated.