The determination of widely used anaesthetic and analgesic drugs in biological fluids is of major clinical importance. Typical methods used for sample preparation employ liquid-liquid extraction protocols which are complex, costly, not handy and not amenable to automation. In the present communication, we report the development of a methodology that employs headspace solid-phase microextraction (HS-SPME) for the determination of four anaesthetic (lidocaine, midazolam, diazepam and ketamine) and three analgesic drugs (fentanyl, remifentanyl and codeine) in human urine. Important parameters controlling SPME were studied: selection of SPME fibre, type and amount of salt added, preheating and extraction time, extraction temperature, sample volume and desorption time. GC with nitrogen phosphorus detection (GC-NPD) facilitates sensitive and selective detection of the anaesthetics. The developed method renders an efficient tool for the precise and sensitive determination of the anaesthetics and analgesics in human urine (RSDs ranged from 7.7 to 12.6%, whereas LODs ranged from 0.01 to 1.5 ng/mL). The method was applied to the determination of the anaesthetics and analgesics in human urine from patients that had undergone coronary by-pass surgery operations. The proposed protocol can function as an attractive alternative for clinical acute intoxications and medico-legal cases.