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We have carried out a systematic review of epidemiological studies about the association between extreme weather conditions and work-related injuries (WRI). Furthermore, we have analysed the association between extreme temperature, air pollutants and WRI in three Italian cities identifying more susceptible workers’ categories by the means of a case cross over study.We have performed a systematic review of epidemiological studies concerning the risk of WRI for extreme temperature. All occupational injuries between 2001–2010 in Milan, Turin and Rome have been extracted from the Italian workers compensation claims archives. Associations between temperature (T), air pollutants (PM10, NO2, O3) and WRI have been estimated using a time-stratified case-crossover study, separately in May-September (warm season, WS) and November-February (cold season, CS).The epidemiological studies for estimating the association between extreme temperature and WRI appeared to be few and conducted with different methodologies. In our study exposure to NO2 (lag 0–8) showed the highest positive effect on the risk of WRI ranging, in the warm season, between +20% (CI 95%: 1.16–1.24) in Milan and +30% (CI 95%: 1.24–1.37) in Turin. Temperature, in WS, was associated to an increased risk of WRI among those working in construction, transport and energy industry with bricklayer, metalworker, mechanic, and asphalter as the most involved workers’ categories. The findings of our study should be considered for planning health and safety prevention programs and correctly identifying measure targeted to risk mitigation for specific categories of workers.