The role of hand hygiene in the prevention of respiratory tract infections in Hajj pilgrims has not been assessed through a focussed systematic review of the literature. To this end, a systematic review was undertaken to synthesize the up-to-date literature on the compliance and effectiveness of hand hygiene among Hajj attendees. Major databases, including OVID Medline, were searched by using a combination of MeSH terms and text words for potentially relevant articles. Data from identified articles were abstracted, quality assessed and combined into a summary effect. Twelve observational studies containing data of 6,320 pilgrims were included. The compliance of hand washing with non-alcoholic surfactants was 77.7% (ranged from 31.5% to 90.3% in individual studies) and the compliance of hand cleaning with alcoholic products was 44.9% (ranged from 30.7% to 67.4%). Education was a key influencer of hand hygiene practice. Only three of six studies that assessed the effectiveness of hand hygiene against clinical disease found the practice to be effective, and only one of two studies that evaluated its effectiveness against a laboratory-confirmed infection found it to be effective. This systematic review suggests that hand hygiene using non-alcoholic products is generally acceptable among Hajj pilgrims but there is no conclusive evidence on its effectiveness.