To investigate clinical settings, management strategies, antibiotic sensitivities, and visual acuity outcomes of endophthalmitis caused by Streptococcus pneumoniae.Retrospective, observational case series.Records were reviewed of all patients with culture-positive endophthalmitis caused by Streptococcus pneumoniae treated at the Bascom Palmer Eye Institute between January 1, 1989 and December 31, 2003.Visual acuity and antibiotic sensitivities.Twenty-seven eyes of 27 patients met study inclusion criteria. The median follow-up was 7 months (range, 3 months to 10 years). Clinical settings included acute postoperative (10 eyes), corneal stitch abscess (5), corneal ulcer (3), bleb-associated (4), post-trauma (3), and endogenous (2). Eighteen cases (67%) were acute-onset (less than 3 weeks from event), with a median interval between event and presentation of endophthalmitis of 5 days (range, 1 day to 16 days). Nine cases (33%) were delayed-onset (median, 27 months; range, 3 to 121 months). Initial visual acuity was hand motions or better in 11 cases (41%). Initial therapeutic procedures included vitreous tap and injection of intravitreal antibiotics in 15 eyes (56%), pars plana vitrectomy and injection of intravitreal antibiotics in 10 eyes (37%), and evisceration in 2 eyes (7%). Seventeen (68%) of 25 eyes received intravitreal dexamethasone. Twelve patients (48%) received additional doses of intraocular antibiotics, and 11 patients (44%) underwent secondary surgical intervention within one week of diagnosis. The Streptococcus pneumoniae isolates showed sensitivity patterns as follows: 27/27 vancomycin, 13/13 clindamycin, 6/6 cefazolin, 11/11 ciprofloxacin, 14/14 moxifloxacin, 24/26 (92%) ofloxacin, 12/14 (86%) levofloxacin, 13/14 (93%) gatifloxacin, and 1/13 (8%) gentamicin. The organism was sensitive to at least one antibiotic administered initially in all cases. Final visual acuity was 20/400 or better in 8/27 (30%) cases, but 10 eyes (37%) had a final vision of no light perception.Despite prompt treatment with appropriate antibiotics, endophthalmitis caused by Streptococcus pneumoniae is associated with a poor visual prognosis.