Benzodiazepines and related drugs (BZDRs) are widely used in the treatment of anxiety and sleep disorders, but cognitive adverse effects have been reported in long-term use, and these may increase the risk of labor market marginalization (LMM). The aim of this study was to investigate whether the risk of LMM is associated with new long-term BZDR use compared to short-term use. This register-based nationwide cohort study from Finland included 37,703 incident BZDR users aged 18-60years who initiated BZDR use in 2006. During the first year of use, BZDR users were categorized as long-term users (≥180days) versus short-term users based on PRE2DUP method. The main outcome was LMM, defined as receipt of disability pension, long-term sickness absence (>90days), or long-term unemployment (>180days). The risk of outcomes was analyzed with Cox regression models, adjusted with sociodemographic background, somatic and psychiatric morbidity, other types of medication and previous sickness absence. During 5 years of follow-up, long-term use (34.4%, N=12,962) was associated with 27% (adjusted Hazard Ratio, aHR 1.27, 95% CI 1.23-1.31) increased risk of LMM compared with short-term use. Long-term use was associated with 42% (aHR 1.42, 95% CI 1.34-1.50) increased risk of disability pension and 26% increased risk of both long-term unemployment and long-term sickness absence. These results indicate that long-term use of BZDRs is associated with increased risk of dropping out from labor market. This may be partly explained by cognitive adverse effects of prolonged BZDR use, which should be taken into account when prescribing BZDRs.