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Background: One of the challenges in early-stage clinical research aimed at developing novel treatments for alcohol use disorder (AUD) is that the enrolled participants are heavy drinkers, but do not seek treatment for AUD., Aims: To compare nontreatment seekers with alcohol dependence (AD) from 4 human laboratory studies conducted at Brown University (N = 240; 65.4% male) to treatment seekers with AD from the multisite COMBINE study (N = 1,383; 69.1% male) across sociodemographic and alcohol-related clinical variables and to evaluate whether the variables that significantly differentiate the 2 samples predict the 3 main COMBINE clinical outcomes: time to relapse, percent days abstinent (PDA), and good clinical outcome., Methods: Sample characteristics were assessed by parametric and nonparametric testing. Three regression models measured the association between the differing variables and the 3 main COMBINE clinical outcomes., Results: The nontreatment seekers, compared to the treatment seekers, were more ethnically diverse, less educated, single, and working part-time or unemployed (p's < 0.05); they met fewer DSM-IV AD criteria and had significantly lower scores on alcohol-related scales (p's < 0.05); they were less likely to have a father with alcohol problems (p < 0.0001) and had a significantly earlier age of onset and longer duration of AD (p's < 0.05); they also had significantly more total drinks, drinks per drinking day, heavy drinking days (HDD), and lower PDA in the 30 days prior to baseline (p's < 0.0001 to <0.05). Having more HDD in the 30 days prior to baseline predicted all of the 3 COMBINE clinical outcomes. All the other characteristics mentioned above that differed significantly between the 2 groups predicted at least 1 of the 3 COMBINE clinical outcomes, except for level of education, age of onset, and duration of AD., Conclusions: The observed differences between groups should be considered in efforts across participant recruitment at different stages of the development of new treatments for AUD., (© 2020 by the Research Society on Alcoholism. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)