<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Disordered gambling (<jats:styled-content style="fixed-case">DG</jats:styled-content>) has often been associated with impaired decision‐making abilities, suggesting a dysfunction in the ventromedial prefrontal cortex (vm<jats:styled-content style="fixed-case">PFC</jats:styled-content>).</jats:p></jats:sec><jats:sec><jats:title>Aims</jats:title><jats:p>To our knowledge, no previous study has accurately considered the effect of substance use disorder (<jats:styled-content style="fixed-case">SUD</jats:styled-content>) comorbidity (including nicotine dependence) on decision‐making impairments in <jats:styled-content style="fixed-case">DG</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Methods and Materials</jats:title><jats:p>We employed the Cambridge Gambling Task (<jats:styled-content style="fixed-case">CGT</jats:styled-content>) to assess a big cohort of patients diagnosed with <jats:styled-content style="fixed-case">DG</jats:styled-content> (<jats:italic>N = 80</jats:italic>) against matched healthy controls (<jats:styled-content style="fixed-case">HC</jats:styled-content>s) (<jats:italic>N = 108</jats:italic>). The cohort included <jats:styled-content style="fixed-case">DG</jats:styled-content> patients with nicotine and alcohol dependence, alcohol dependence only and 12 “pure” nonsmokers with only <jats:styled-content style="fixed-case">DG</jats:styled-content> diagnosis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:italic>Pure</jats:italic> nonsmoking, nicotine dependent as well as alcoholic <jats:styled-content style="fixed-case">DG</jats:styled-content>s with current nicotine dependence, demonstrated a decision making profile, characterized by poor decision‐making abilities and failure to make right choices (rational), closely resembling that of patients with vm<jats:styled-content style="fixed-case">PFC</jats:styled-content> damage.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>This suggests that <jats:styled-content style="fixed-case">DG</jats:styled-content>s with and without <jats:styled-content style="fixed-case">SUD</jats:styled-content> comorbidity are equally affected in that domain of decision making abilities. Additionally, gambling diagnosis combined with alcohol and nicotine dependence involves a group of gambling patients with a relatively riskier decision making profile, showing that these patients apart from making irrational decisions take also more risks. Our findings highlight the importance of accounting for <jats:styled-content style="fixed-case">SUD</jats:styled-content> comorbidities with useful implications for future research and therapy. Limitations of the current investigation are discussed.</jats:p></jats:sec>