ObjectiveTo identify the factors associated with fatal occupational injuries in Mexico in 2012 among workers affiliated with the Mexican Social Security Institute.MethodsAnalysis of secondary data using information from the National Occupational Risk Information System, with the consequence of the occupational injury (fatal versus non-fatal) as the response variable. The analysis included 406,222 non-fatal and 1,140 fatal injuries from 2012. The factors associated with the lethality of the injury were identified using a logistic regression model with the Firth approach.ResultsBeing male (OR=5.86; CI95%: 4.22-8.14), age (OR=1.04; CI95%: 1.03-1.06), employed in the position for 1 to 10 years (versus less than 1 year) (OR=1.37; CI95%: 1.15-1.63), working as a facilities or machine operator or assembler (OR: 3.28; CI95%: 2.12- 5.07) and being a worker without qualifications (OR=1.96; CI95%: 1.18-3.24) (versus an office worker) were associated with fatality in the event of an injury. Additionally, companies classified as maximum risk (OR=1.90; CI 95%: 1.38-2.62), workplace conditions (OR=7.15; CI95%: 3.63-14.10) and factors related to the work environment (OR=9.18; CI95%:4.36-19.33) were identified as risk factors for fatality in the event of an occupational injury.ConclusionsFatality in the event of an occupational injury is associated with factors related to sociodemographics (age, sex and occupation), the work environment and workplace conditions. Worker protection policies should be created for groups with a higher risk of fatal occupational injuries in Mexico.