Carpal tunnel syndrome (CTS), the commonest nerve entrapment syndrome, is one of the most frequent occupational disorders related to manual work. Both occupational and personal risk factors make it difficult to recognize the true origin of its occurrence and to devise prevention strategies. Most of the information available about occupational CTS originates from cross-sectional studies on various job titles, where the prevalence of the disease has been reported to vary between 0.6% and 61%. Few longitudinal studies are available on occupational CTS. Consensus has been reached about the criteria to diagnose CTS in epidemiological studies. However, different methods are used by different investigators to assess exposure to repetition and force, the two factors which appear to be most important in originating the disease. This could help explain the difficulty in establishing a sound exposure-effect relationship (an indispensable basis for setting exposure limits). To help fill the gap in knowledge regarding occupational CTS incidence and its relationship to occupational exposure we are performing a large longitudinal multisector study, denominated OCTOPUS. OCTOPUS has been designed to assess the incidence of CTS in a large cohort of workers employed in different sectors and exposed to different level of repetitive and forceful manual work and to relate the incidence of the disease to the possible casual factors and their variation over time. Herein, the study protocol is described.