Purpose To track the relative frequency and explore possible risk factors of fungal compared with bacterial endophthalmitis after corneal transplantation. Design Case-comparison study nested in a surveillance registry. Methods We examined, among recipients who underwent surgery from January 1991 through December 2003, demographic and eye-banking characteristics of postkeratoplasty endophthalmitis cases that were reported to the Eye Bank Association of America by US eye banks. Potential predictors of fungal compared with bacterial endophthalmitis were examined using multiple logistic regression. Results Of 234 reported cases of postkeratoplasty endophthalmitis reported by US eye bank, 46 cases (19.7%) were fungal, and 130 cases (55.6%) were bacterial. Concordant cultures of the residual donor corneoscleral rim or preservation medium occurred significantly more often with fungal than bacterial endophthalmitis ( P = .009). After the introduction of Optisol-GS, the odds of bacterial relative to fungal endophthalmitis decreased by 77% (95% confidence interval, 44% - 91%). After adjustment for the preservation method and other eye-banking variables, the odds of fungal endophthalmitis was 3.4 (95% confidence interval, 1.6 - 7.4) times that of bacterial endophthalmitis, when donor corneal preservation was 4 days or longer. Conclusions The frequency of postkeratoplasty bacterial endophthalmitis compared with fungal endophthalmitis fell after widespread use of a corneal preservation medium supplemented with gentamicin and streptomycin. Further improvements in corneal preservation procedures are needed.