BACKGROUND Everolimus can be utilized after heart or lung transplantation to reduce calcineurin inhibitor associated nephrotoxicity, due to cell cycle inhibitor adverse effects, and as adjunct therapy for rejection, cardiac allograft vasculopathy, and bronchiolitis obliterans syndrome. MATERIAL AND METHODS A single-center, retrospective cohort study was conducted including 51 adult heart transplant patients (n=32) and lung transplant patients (n=19) started on everolimus due to immunosuppressive therapy intolerance or failure, between 2010 and 2017. Everolimus indication, response, efficacy, and tolerability were assessed. RESULTS Everolimus was most commonly initiated due to leukopenia/neutropenia (n=17, 33%) or renal dysfunction (n=13, 25%). Leukopenia/neutropenia resolved in 76% of patients (13 out of 17 patients). Renal function (GFR) increased 7.4 mL/min from baseline to 3 months after everolimus initiation (P=0.011). The most common adverse effects were edema (n=23, 45%) and hyperlipidemia (n=25, 49%). A high discontinuation rate was observed (n=21, 41%), mostly from edema. CONCLUSIONS Everolimus might be beneficial in heart and lung transplant patients with leukopenia or neutropenia and lead to modest, short-term renal function improvement. Patient selection is crucial because adverse effects frequently lead to everolimus discontinuation.