BACKGROUND Tacrolimus, a calcineurin inhibitor, is the cornerstone of immunosuppressive strategies in transplantation. Other studies have concluded that hyperkalemia correlates with tacrolimus therapy, though the impact is poorly understood. In 2 separate analyses, the aim of this study was to investigate if the presence and/or magnitude of exposure to tacrolimus increased potassium levels in heart or lung transplant recipients. MATERIAL AND METHODS This retrospective study identified allograft recipients who underwent heart or lung transplantation from January 2013 to December 2019 at Ochsner Health in New Orleans, USA. The first analysis (A-1) comprised 103 lung transplant patients' assessed potassium levels and prevalence of hyperkalemia in the absence of tacrolimus before transplant versus 30 days after transplant on tacrolimus. The second analysis (A-2) included 187 heart or lung transplant recipients and compared potassium levels and prevalence of hyperkalemia at day 30 after transplant during higher tacrolimus exposure (High-TAC) vs day 300 during lower tacrolimus exposure (Low-TAC). RESULTS In A-1, patients on tacrolimus had higher median potassium (4.7 mmol/L vs 4.1 mmol/L, P<0.0001) and prevalence of hyperkalemia (32.04% vs 5.83%, P<0.0001). In A-2, patients in the High-TAC group had higher median potassium (4.6 mmol/L vs 4.4 mmol/L, P=0.0005) and prevalence of hyperkalemia (22.46% vs 12.30%, P=0.0056). CONCLUSIONS Our findings support those from previous studies. Presence of and higher levels of tacrolimus were associated with hyperkalemia following heart and lung transplantation. These findings highlight the importance of long-term monitoring of potassium levels in patients treated with tacrolimus.