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Accidents at work are a major concern because of their social and economic impact. The causes are highly variable and often linked to risk behaviors that could be avoided, of which substance use is a prime example. The aim of this paper was to meta-analytically review the scientific literature on substance intake and its link to work-related accidents. From an initial pool of 19954 papers, we considered a final sample of 27 clustered in three groups according to substances class (alcohol, recreational drugs, medicines). Despite different pharmacological effects, substances consumed for recreational purposes significantly increased the risk of work-related accidents (odds ratio: alcohol 1.78, recreational drugs 1.47), whereas medicines did not: however, these results require caution due to the heterogeneity of the included studies and suspected publication bias. While bio-psycho-social factors could have helped to understand this association, selected studies neglected both the variegated effects and the root causes of recreational substance consumption. Future studies and interventions should consider these complexity factors to transcend the mere description of the phenomenon.