Background <p>To review the histopathological diagnoses, visual outcome, and complications of orbital biopsy in a UK tertiary referral centre.</p> Methods <p>This was a retrospective, clinico–pathological, interventional, consecutive case series. All orbital biopsies performed between January 2004 and December 2023 in Newcastle Eye Centre were included. Data collected from the local electronic database and medical records were analysed. The study was divided into Period 1 (2004-2013) and Period 2 (2014-2023) for descriptive and analytic purposes.</p> Results <p>A total of 338 orbital biopsies were identified during the study period: 180 patients (55.2%) were female and the mean age was 54.6 ± 20.2 years. Orbital biopsies were performed unilaterally in 314 (96.3%) patients and bilaterally in 12 (3.7%) patients. The two most common histopathological diagnoses were non-specific inflammatory disease (102, 31.3%) and lymphoma (85, 26.1%). Amongst cases classified as inflammatory disease, there was a significant increase in the IgG4 disease from Period 1 (2, 3.6%) to Period 2 (9, 15.8%; <i>p</i> = 0.029). The distribution of other diagnoses remained similar between the two periods. One patient (0.3%) experienced a ≥ 2 Snellen line drop in vision following biopsy. There were 14 (4.3%) patients with postoperative complications, the most common being diplopia (7, 2.1%). Postoperative diplopia was associated with posterior lesion (<i>p</i> = 0.045), lateral orbitotomy (<i>p</i> = 0.015) and excisional biopsy (<i>p</i> &lt; 0.001).</p> Conclusion <p>This study has not only shown orbital biopsy to be a safe an effective tool but also highlights an increase in IgG4 diagnosis. It has also identified significant risk factors for complication following orbital biopsy.</p>