The current study investigated the night-to-night variability and diagnostic accuracy of the oxygen desaturation index (ODI), as measured by ambulatory monitoring, in the diagnosis of mild and moderate obstructive sleep apnoea–hypopnoea syndrome.To assess the variability of the ODI, 35 patients were monitored at home during 7 consecutive nights by means of a portable recording device, the MESAM-IV®. The ODI variability factor and the influence of age, body mass index (BMI), alcohol, and body position were assessed. Furthermore, the diagnostic accuracy of the MESAM-IV was measured by comparison with polysomnographical outcomes in 18 patients.During home recording, the median ODI was 10.9 (interquartile range: 5.8–16.1) across the patients. Although the reliability of the ODI was adequate, the probability of placing the patient in the wrong severity category (ODI ≤15 or ODI >15) when only one single recording was taken is 14.4%. ODI variability was not significantly influenced by age, BMI, time spent in a supine position, or mild dosages of alcohol. A good correlation was found between the apnoea–hypopnoea index and the ODI.In conclusion, the findings suggest that the diagnostic accuracy of the MESAM-IV is strong, since the oxygen desaturation index is correlated with the apnoea–hypopnoea index. In most obstructive sleep apnoea–hypopnoea syndrome patients, oxygen desaturation index variability is rather small, and screening could be reliably based on single 1-night recordings.