Chronic Toxoplasma gondii (T. gondii ) infection is known to trigger potentially adverse immuno-regulatory changes, but the long-term implication for heart transplant (HTx) recipients has not been assessed previously. Hence, we evaluated the risk of mortality, development of cardiac allograft vasculopathy (CAV) and acute cellular rejection amongst T. gondii seropositive HTx recipients and the four donor/recipient seropairing groups. Methods: Frozen pre-HTx serum samples of 288 recipients and 246 donors were evaluated for T. gondii serostatus using Platelia IgG immunoassay method. All patients had also undergone prospective serostatus evaluation using alternative assays and results determined by the two methods were compared. Follow-up data regarding mortality, CAV development and acute cellular rejection was available for all patients. Results: Overall, 211 (73%) recipients were seronegative and 77 (27%) were seropositive. In total, 82 recipients died, 76 developed CAV and 82 had significant cellular rejection. Recipient seropositivity was associated with a significantly higher risk of all-cause mortality (hazard ratio [HR], 1.9; 95% CI, 1.1–3.4; p= 0.02) and CAV mortality (HR=4.4; 95% CI, 1.3–15.6, p=0.02), but was not associated with earlier CAV development or higher rejection score. Donor/recipient seropairing status was not a risk factor for any endpoint. Conclusions: T. gondii seropositivity amongst HTx recipients is associated with a significantly increased risk of long-term total, and in particular CAV-related, mortality. This may be mediated via immunoregulatory changes triggered by chronic T. gondii infection and needs to be explored further.