Adolescence is a life stage characterized by physical, social, and emotional changes including a shift towards peer orientation and an explorative approach to substance use. Previously, we identified distinct adolescent substance use patterns. Here we characterized adolescents with distinct patterns of substance use and tested whether patterns were associated with acute outcomes. Data from the Danish National Youth Cohort 2014, comprising 68 301 participants aged 15-19 years attending upper secondary education, were used. Previously identified substance use patterns were Alcohol Only (48.8%), Frequent Binge Drinking (23.3%), Experimental Use (16.3%), and Early Multiple Use (11.6%). Adolescents with distinct substance use patterns were characterized by adverse childhood experiences, social networks, parental support, and mental health. Associations between patterns and the risk of unintentional injury, violence, and mortality were assessed over an 8.2-year follow-up period. An accumulation of adverse childhood experiences, lack of parental support and poor mental health were observed in adolescents with most substance use. Substance use patterns were associated with the risk of unintentional injury, violence, and mortality in a dose-dependent manner. For instance, compared to Alcohol Only, hazard ratios (95% CI) for severe unintentional injury were 1.25 (1.08-1.44), 1.40 (1.17-1.66), 1.50 (1.25-1.79) for adolescents with Frequent Binge Drinking, Experimental Use, and Early Multiple Use. Adolescent substance use patterns were associated with short- and long-term risks of acute health outcomes. Additionally, disadvantages cluster in adolescents with more substance use, highlighting the aggregation and potential interaction of challenges faced by vulnerable subgroups that extend into adulthood.