Xeroderma Pigmentosum (XP) is a rare autosomal recessive disease, caused by a molecular defect in nucleotide excision repair (NER) genes. These patients present with many perioperative anaesthetic challenges like difficult venous cannulation, difficult intubation due to facial and oropharyngeal changes, difficult extubation due to epiglottis subsidence, prolonged action of neuromuscular blocking agents and increased sensitivity to opioids.Harmful effects of inhalational anaesthetic agents on nucleotide excision repair has been proposed. Planned airway management is necessary, short acting opioids with the use of multimodal analgesia is preferred and total intravenous anaesthesia (TIVA) is preferred to inhalational anesthetics. The novel anaesthetic agent Dexmedetomidine, alpha-2 agonist could be a valuable anaesthetic adjunct to TIVA. Besides, it also reduces the induction and maintenance dose of propofol, blunts the airway reflex during intubation and extubation, decreases the requirement of opioids and also helps to enhance the recovery. We present 3 cases of XP, who underwent surgery using propofol and dexmedetomidine infusion, without the use of muscle relaxants and inhalational agents.