Benzodiazepines (BZDs) are widely used psychotropic agents, prescribed primarily for anxiety, insomnia, epilepsy, alcohol withdrawal, and palliative care. Despite their therapeutic benefits, their long-term use is associated with dependence, cognitive decline, adverse drug reactions (ADRs), and increased mortality, particularly among older adults and in polypharmacy contexts. Over recent decades, regulatory authorities in England have issued guidelines to restrict long-term prescribing, while public health campaigns have promoted deprescribing. The COVID-19 pandemic introduced further complexity, with widespread mental health deterioration and changes in healthcare delivery potentially influencing prescribing practices and related outcomes. The existing literature provides fragmented insights, often limited to discrete populations or short timeframes, leaving gaps in understanding long-term national trends of benzodiazepine prescribing, demographic disparities, and correlations with outcomes. This thesis presents a retrospective observational pharmacoepidemiological analysis of national prescribing and safety data for 14 benzodiazepines in England between 2017 and 2025. Data sources included the English Prescribing Dataset (EPD), NHS Business Services Authority (NHSBSA), Open Prescribing, and the Medicines and Healthcare products Regulatory Agency (MHRA) Yellow Card Scheme. Prescribing trends were standardised per 100,000 population and stratified into pre-pandemic, pandemic, and post-pandemic phases. Statistical analyses comprised descriptive trends, linear regression modelling, and stratified regression by deprivation, age, gender, and ethnicity. Mortality and ADR outcomes were evaluated through temporal association with prescribing data, and NHS expenditure was analysed to identify anomalies in drug costs. Overall, benzodiazepine prescribing declined during the study period, driven by reductions in diazepam, temazepam, and chlordiazepoxide. However, prescribing of clobazam increased substantially; clonazepam rose modestly, and midazolam hydrochloride showed regionally concentrated growth, particularly in palliative care. The COVID-19 pandemic was associated with a temporary reduction in prescribing volumes but a marked increase in ADRrelated fatalities, notably for oxazepam, nitrazepam, temazepam, and diazepam. Post-pandemic, prescribing stabilised at lower levels, but mortality rates remained elevated for several agents. Socioeconomic and demographic analysis revealed significant disparities. Higher prescribing rates were observed in deprived, predominantly white regions, while ethnically diverse deprived areas exhibited lower prescribing despite comparable or greater mental health burdens. Women accounted for approximately two-thirds of prescriptions, and older adults remained the most persistent long-term users, facing heightened risks of falls, fractures, and cognitive decline. Economic analysis demonstrated stable overall expenditure but revealed a striking anomaly: the costs of temazepam rose by more than 200% despite declining prescription volumes, indicating vulnerabilities in the pricing and supply chains of the drug. Safety analysis revealed lorazepam as a critical concern, with statistically significant increases in severe or fatal ADRs even as prescribing volume decreased. These findings demonstrate that national deprescribing initiatives have succeeded in reducing the traditional use of anxiolytic and hypnotic BZDs. Yet, prescribing has shifted towards specialist-use drugs, driven by clinical necessity and evolving therapeutic practices. The pandemic exacerbated risks, with reduced access to non-pharmacological therapies and increased reliance on pharmacological solutions contributing to elevated mortality and ADR rates. Persistent regional and socioeconomic inequalities suggest that prescribing is shaped not only by clinical demand but also by structural inequities in access to mental health care. The anomalous rise in temazepam expenditure highlights the need for policy attention to drug pricing regulation, while lorazepam’s disproportionate ADR profile calls for enhanced pharmacovigilance. Benzodiazepine prescribing in England between 2017 and 2025 shows an overall decline, yet the therapeutic and safety landscape has grown increasingly complex. Specialist-use BZDs such as clobazam and midazolam are rising in prominence; socioeconomic and ethnic disparities remain entrenched, and ADRs and mortality continue to pose serious risks, especially post-pandemic. The unexpected escalation in drug costs highlights vulnerabilities in the NHS medicines budget. These findings necessitate an integrated policy response that balances patient safety, clinical necessity, and equitable access to care. Future research should explore prescriber decision-making, patient withdrawal experiences, and long-term safety outcomes. This thesis contributes to a comprehensive national analysis, closing critical evidence gaps and providing a framework for guiding clinical practice, public health policy, and future pharmacoepidemiologic research.