Background: Microbial Keratitis (MK) is the leading cause of unilateral blindness after cataract in Tropical regions and is responsible for 2 million cases of blindness per year. In Sub-Saharan Africa, MK is a neglected problem, most ophthalmic centres do not have diagnostic services, patients present late, appropriate drugs are often not available, corneal transplant services are rarely available. Subsequently, outcomes are poor in this area. Currently there are very limited data to guide policy and practice. Methods: In a main cohort design, individuals with MK presenting to the two referral eye hospitals in South Western Uganda were enrolled over a one-year period. Clinical history and presentation journey were recorded. Their eyes were carefully examined, and samples were collected for microbiology. Patients were tested for HIV and Diabetes. At three months, patients were followed up in their homes and at this point healthy community controls were enrolled to compare risk factors in a nested case-control study and assess the impact of the disease on the Quality of Life (QoL). A separate situation analysis survey of lower health centres was additionally conducted to understand the role of the health system in management of MK. Results: Three hundred and thirteen individuals were enrolled. Median age was 47 years (ra nge 18-96) and 174 (56%) were male. Median presentation time to the eye hospital was 17 days from onset (IQR 8-32). Trauma was reported by 29%. Majority presented with severe in fections (median infiltrate size 5.2 mm); 47% were blind in the affected eye (vision <3/60), fu ngal cases were 62%. At 3-months, 30% of participants were blind in the affected eye, while 9% had lost their eye from the infection. Predictors of poor vision at 3-months were: baseline vision (aOR 2.98 [95%CI 2.12-4.19], p<0.0001), infiltrate size (aOR 1.19 [95%CI 1.03-1.3 6], p<0.020) and perforation at presentation (aOR 9.93 [95% CI 3.70-26.6], p<0.0001). Traditional Eye Medicine (TEM) use was reported in 188/313. TEM users had a delayed presentation; median presenting time 18 days versus 14 days, p= 0.005; had larger ulcers 5.6 mm versus 4.3 mm p=0.0005; a worse presenting visual acuity median logarithm of the minimum angle of resolution (Log MAR) 1.5 versus 0.6, p=0.005; and, a worse visual acuity at 3 months median Log MAR 0.6 versus 0.2, p=0.010. In the qualitative analysis, reasons for TEM use included lack of confidence in conventional medicine, health system breakdown, poverty, fear of the eye hospital, cultural belief in TEM, influence from traditional healers, personal circumstances and ignorance. In the case-control analysis, HIV OR 83.5 (95%CI 2.01-3456), p=0.020, Diabetes OR 9.38 (95% CI 1.48-59.3), p=0.017 and a farming occupation OR 2.60 (95%CI 1.21-5.57), p=0.014 were main risk factors of MK. In the Quality of Life (QoL) analysis, mean QoL scores of the cases were lower than controls across all domains. Determinants of QoL among the cases at 3-months included visual acuity at 3-months and history of eye loss. Although most patients presented early to the primary health centres (median 2days IQR 0-5 days), there were severe weaknesses along the health system in identification and early referral of MK. Only 12% of the health workers could make a diagnosis of MK. None of the health facilities had a stock of the recommended first line treatment options for MK (ciprofloxacin and Natamycin eye drops). Conclusion: This is the first large epidemiological cohort in SSA studying MK and provides a baseline understanding of the epidemiology, aetiology and outcomes, and what needs to be done to improve the situation and reduce the devastating visual outcomes currently experienced by many people