Background The age of onset of substance use (OSU) as well as the coping strategies (CS) influence both the development and the course of Substance Use Disorders (SUD). We aim to examine the differences in the CS applied to deal with treatment in men with SUD, considering whether the age of OSU had begun at age 16 or earlier (OSU ≤ 16) or at 17 years or later (OSU ≥ 17), as well as the associations of the CS with clinical variables were studied. Methods A total of 122 patients with at least three months of abstinence, 60 with OSU≤16 and 62 with OSU≥17, were evaluated through the Coping Strategies Inventory and clinical assessment tools. Results The OSU≤16 patients were younger and presented a worse clinical state. Compared to the norms, the SUD patients were less likely to use adaptive CS, although this was more remarkable for the OSU≤16 group. Furthermore, the OSU≤16 patients presented a CS pattern of higher Disengagement, with lesser use of Social Support and higher Problem Avoidance and Social Withdrawal. In the whole SUD sample, the severity of addiction, number of relapses and age of OSU (as a continuous variable) were related to maladaptive coping. Nevertheless, the cut-off age of OSU modulated these results. Conclusions The OSU≤16 was a risk factor for presenting greater clinical severity and a more dysfunctional CS profile to deal with treatment. Thus, the cut-off age considered has allowed us to differentiate SUD patients with more vulnerability to present worse clinical prognosis who may require specific prevention and rehabilitation strategies discussed throughout this work.