Peri-operative management of patients with significant cardio-respiratory disease scheduled for non-cardiac non-thoracic surgeries requires great expertise to ensure a successful outcome. Patients with cardio-respiratory diseases are prone to developing some intra-operative complications such as delayed recovery from anaesthesia, persistent poor arterial oxygen saturation, haemodynamic instability, myocardial ischaemia, arrhythmias or cardiac arrest. The aim of this case series is to present our experience of anaesthetic management of five patients with multiple co-morbid cardio-respiratory diseases who had surgeries in the presence of severe respiratory and cardiovascular systems compromise. The anaesthetic technique of choice was titrated-dose epidural anaesthesia with hyper-vigilant monitoring, rational use of vasoconstrictor agents and restrictive intraoperative fluid administration. Except for episodes of hypotension in three of the patients which responded to vasoconstrictors, the outcomes were excellent and patients and surgeons were satisfied.