Objective: To assess the compliance with hand hygiene guidelines among nursing staff in secondary care hospitals in Kuwait. Subjects and Methods: A cross-sectional study was conducted through direct observation using the Lewisham observation tool and self-administered questionnaire in six major public secondary care hospitals in Kuwait. Only patient care activities that are described as ‘dirty contacts’ by the Fulkerson scale were considered as indications for hand hygiene while any attempt for hand hygiene was considered as compliance. A self-administered questionnaire was prepared and pilot tested and then distributed to nursing staff at each ward immediately after conducting the inspection; 550 were distributed and 454 were completed and returned. Among 204 observation sessions, a total of 935 opportunities and 312 hand hygiene practices were recorded. Results: The overall compliance was 33.4%. The observed compliance significantly varied between different ward categories from 14.7% in emergency to 55% in medical wards. Of the 454 nursing staff who participated in self-reported compliance, 409 (90%) indicated that they always washed their hands upon practicing patient care activities. Nurses consistently reported higher compliance after conducting patient care activities rather than before. Being busy with work (42.2%), having sore/dry hands (30.4%) and wearing gloves (20.3%) were the most frequently reported hindrances to improving hand hygiene. Conclusion: Observed hand hygiene compliance among nursing staff in secondary care hospitals in Kuwait was poor. High self-reported compliance may reflect a high level of awareness of hand hygiene but may also suggest that improving compliance through increasing awareness has probably reached saturation.