Anterior uveitis is the most common form of uveitis in most regions of the world. A recent study reported that 50 % of patients with anterior uveitis have a related systemic illness. The most common cause of anterior uveitis to date remains idiopathic (45-50 %), followed by HLA-B27-positive acute anterior uveitis. Ours is a retrospective study of the clinical records of 42 patients with anterior uveitis seen at a tertiary care eye hospital in south India. To diagnose the associated systemic disease, the investigations carried out were erythrocyte sedimentation rate, red and white blood cell counts, anti-nuclear antibody (ANA) analysis and HLA-B27 antigen determination. Based on clinical features, patients were also investigated for serum angiotensin-converting enzyme, high-resolution computed tomography scan, Mantoux test and QuantiFERON-TB Gold test. American College of Rheumatology criteria were followed to diagnose spondyloarthropathies and juvenile idiopathic arthritis (JIA). Of the 42 patients, 14 (33.33 %) were HLA-B27-positive and the remaining 28 (66.66 %) HLA-B27-negative. Overall, 32 of the 42 had no causative association, three patients were diagnosed with JIA, two with ankylosing spondylitis, two were associated with systemic tuberculosis, two with sarcoidosis and one with Vogt-Koyanagi-Harada syndrome. Our case series shows the incidence of various systemic diseases associated with anterior uveitis. Though the overall incidence of HLA-B27-positive acute anterior uveitis in our series (33 %) is similar to that in the Western literature, only 14 % of such patients were positive for a spondyloarthropathy. A few interesting cases like HLA-B27-positive, ANA-negative JIA presenting with chronic persisting anterior uveitis were also seen.