Higher birth order is associated with increased risks of adverse health outcomes attributable to alcohol or narcotics in adolescence, but it remains unclear whether these observed birth order effects are also present in midlife. Drawing on a national Swedish cohort born in 1953 and their siblings, we estimate associations between birth order and alcohol- or narcotics-attributable hospitalization or death with a 25-year follow-up to assess whether birth order differences are observed during this life course period. Health events attributable to alcohol or narcotics use were identified using the Swedish National Patient and Cause of Death registers, respectively. We apply Cox proportional hazards models to estimate average birth order differences in hazards for alcohol- or narcotics-attributable hospitalization or death between ages 30 and 55. We estimate birth order differences between families, and use two fixed-effects approaches to estimate birth order differences within families and within families of the same type. Bivariate results indicate increased hazards for both outcomes with higher birth order; however, these results are no longer observed after adjustment for familial background characteristics in all models. Our results thereby show limited evidence for birth order differences in midlife. This study highlights that shared factors within the family of origin may be stronger predictors of adverse health outcomes attributable to substance use among siblings during this life course period. Future research should disentangle the contributions of the social environment within the family of origin for adverse health outcomes attributable to alcohol or narcotics among siblings.