Background: Problematic high-dose benzodiazepine (BZD) and related Z-drug use for a long period is a substance use disorder previously found to be associated with adult attention-deficit/hyperactivity disorder (ADHD) and worse quality of life (QoL). Whether adult ADHD impacts QoL in high-dose BZD/Z-drug users has not been explored. Aim: The aim of the study was to explore the impact of adult ADHD on QoL in high-dose BZD and related Z-drug users. Methods: We recruited 393 patients (205 men and 188 women) consecutively admitted to the Department of Medicine, Addiction Medicine Unit, Verona University Hospital, Italy, from July 2016 to July 2019 for detoxification from high-dose BZD or Z-drug dependence. Demographic and clinical variables and QoL measures were recorded. The World Health Organization ADHD Self-Report Scale version 1.1 Symptom Checklist Part A was used to detect adult ADHD. Results: In our sample, 39.4% of patients were positive to adult ADHD testing (ADHD+), with some clinical features differing in comparison to patients negative to ADHD testing (ADHD−). QoL was worse in high-dose BZD/Z-drug users than the general population. The ADHD+ group showed significantly worse QoL measures than the ADHD− group. Multivariate analysis, including potential covariates showed adult ADHD and age to have the most robust and consistent positive effect for age (i.e., higher QoL) and negative effect for ADHD (i.e., lower QoL) on QoL measures. Conclusions: Adult ADHD is associated with worse QoL measures in high-dose BZD/Z-drug users. Future studies should explore whether appropriate BZD/Z-drug detoxification might improve QoL measures and whether the most appropriate detoxification protocol differs in ADHD+ versus ADHD− populations.