Background <p>Management of endogenous endophthalmitis (EE) is challenging. <i>Klebsiella</i> EE, in particular, carries a guarded prognosis and poor visual outcome. We aimed to test the hypothesis that a certain group of <i>Klebsiella</i> EE would carry a better prognosis when presenting with specific signs, compared to the worse-performing group when treated with initial systemic and intravitreal therapy.</p> Methods <p>A retrospective cohort study was conducted across two local tertiary hospitals to review all cases of <i>Klebsiella</i> EE from January 2013 to December 2022. Anatomical success was defined by retention of the globe, without intractable retinal detachment or phthisis bulbi. Functional success was defined as achieving a visual acuity of better than 1.3 logMAR.</p> Results <p>A total of 56 proven cases of EE were identified. 31 subjects (55.4%) had <i>Klebsiella</i> EE. Of those, 31 eyes of 21 subjects met the inclusion criteria. 4 subjects were unconscious or cognitively impaired at initial presentation. The factors that predict a higher chance of successful treatment with systemic antibiotics and intravitreal antibiotics only, in the <i>Klebsiella</i> EE group, were a better visual acuity at presentation, lack of conjunctival injection, absence of corneal edema, hypopyon, panophthalmitis, and the presence of a fundal view (<i>p</i> &lt; 0.02). The probability of overall treatment success was greater than 50% if the initial visual acuity was better than or close to finger counting at one meter (<i>p</i> = 0.006).</p> Conclusion <p>Universal screening of patients with <i>Klebsiella</i> infection and the identification of earlier EE presentation with these prognostic factors that predict a positive or less severe outcome are crucial for the prompt initiation of treatment within this narrow therapeutic window.</p>