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Objectives: The objective of our study was to evaluate medication-related safety, tolerability and preliminary effectiveness of short-term benzodiazepine tapers to manage atypical withdrawal syndromes among individuals with opioid use disorder (OUD) exposed to the toxic unregulated drug supply containing high levels of non-pharmaceutical fentanyl and benzodiazepines. Methods: We present a case series of individuals with OUD accessing hospital-based withdrawal-management services (N = 18) who were prescribed a benzodiazepine taper alongside medications for OUD (MOUD) in Vancouver, Canada between October 2023 and July 2024 (NCT06639373).Data were collected through baseline questionnaires (i.e., sociodemographic characteristics) and chart reviews; descriptive statistics are reported. Results: Among the 18 participants receiving benzodiazepine tapers, the median age of participants was 30.5 years (IQR 23.8, 44.3), 11 were male, and 8 were unstably housed. All participants received diazepam. The mean total diazepam dose per patient was 93.2 mg (SD 55.7 mg) and the mean duration of the tapers was 5.61 days (SD 3.11). The mean maximum and minimum daily diazepam doses administered were 30.3 mg (SD 13.7 mg) and 7.9 mg (SD 2.5 mg). No medication-related adverse events or tolerability issues were reported. Among participants who completed withdrawal-management (n = 11), the majority (n = 8) remained on therapeutic doses of MOUD continuously for 30-days following discharge. One-third of patients (n = 6) had a patient-initiated discharge event. Conclusions: Short-term benzodiazepine tapers may be a useful adjunct to MOUD in managing complex withdrawal syndromes due to an increasingly adulterated drug supply. Further research on screening, diagnosis, and withdrawal management for this challenging clinical scenario is needed.