Abstract Background The purposes of the study were first to determine the incidence rate of medical unfitness for work at sea among French seafarers, second to identify the conditions (diseases or accidents) causing such incapacity so as to set up prevention measures where possible and third to ascertain whether there were any overrepresentations of diseases according to category of unfit seafarers (fishers, merchant seafarers, shellfish farmers and professional sailors). Methods An exhaustive, observational, descriptive, retrospective epidemiological and nosological study was carried out based on the medical coding of files stored in the Aesculapius® national database, which registers all medical data regarding seafarers presenting at the French seafarers’ health services. The increasing rate of permanent medical unfitness for work at sea was calculated in relation to the annual number of registered seafarers. A 12-year span was chosen in an attempt to ascertain the different sociodemographic categories associated with incapacity. Results In all, 2392 seafarers were declared unfit for work at sea. This represents a permanent medical unfitness for work at sea incidence rate of below 1% for all French seafarers examined for medical fitness between 2005 and 2016. The average age of the population of unfit seafarers was 48. The average time spent at sea before being declared unfit for work at sea was 15.5 years. Sixty-seven percent of the seafarers declared unfit had been working in the fishing sector. The main reasons for deciding permanent unfitness for work at sea were: rheumatological conditions associated specifically with the spine; injuries relating to accidents or other external causes, mostly affecting the upper limbs; mental and behavioural disorders, including mood disorders and particularly addictions; and diseases of the circulatory system, namely coronopathies. The incidence rate of medical unfitness for work at sea was seen to increase between 2005 and 2016, but a decrease due to the dilution effect was noted in 2015. Conclusions Permanent unfitness seldom occurs among French professional seafarers. Prevention measures must be focused on musculoskeletal disorders, psychiatric affections and coronary conditions as well as on combatting maritime accidents, especially in the professional fishing sector, where such affections and accidents are overrepresented.