Sequential bilateral single lung-liver transplantation (SBSL-LTx) is a therapeutic option for patients with end stage lung and liver disease (ESLLD) due to cystic fibrosis (CF). A few cases have been reported, all of them were performed with the use of cardio-pulmonary by-pass (CPB). We performed SBSL-LTx in three young men affected by CF. All the recipients had respiratory failure and portal hypertension with hypersplenism. Along with lung transplants, two patients received a whole liver graft and one an extended right graft from an in situ split liver. During transplantation neither CPB nor veno-venous by-pass (VVB) were employed. Immunosuppression was based on basiliximab, tacrolimus, steroids and azathioprine. The three recipients are alive with a median follow-up of 670 days (range 244–1533). Combined SBSL-LTx is a complex but effective procedure for the treatment of ESLLD due to CF, not necessarily requiring the use of CPB or VVB.