OBJECTIVE This study aimed to compare the surgical outcomes of mitomycin C trabeculectomy glaucoma drainage device (GDD) surgery and laser neodymium:YAG (Nd:YAG) cyclophotocoagulation (CPC) in the management of intractable glaucoma after penetrating keratoplasty (PKP) in a retrospective study. METHODS Interventional case series. METHODS The medical charts of consecutive patients who had pre-existing glaucoma or who developed glaucoma after PKP and underwent a surgical procedure to control the glaucoma at the University Eye Associates of Boston University Medical Center, New England Eye Center, and Massachusetts Eye and Ear Infirmary between January 1991 and July 1995 were reviewed. Follow-up ranged from 6 months to 4 years after the glaucoma procedure. A total of 38 patients were included consisting of 17 patients who underwent mitomycin C, 10 patients who underwent GDD surgery, and 11 patients who had CPC. METHODS Mitomycin C trabeculectomy, GDDs, or Nd:YAG CPC to control glaucoma after PKP was performed, METHODS Graft status, postoperative intraocular pressure (IOP), and visual acuity were the main outcome measures. RESULTS There were no differences among the three groups with respect to the follow-up time after the corneal graft operation (P = 0.15) or after the glaucoma operation (P = 0.98). At the final follow-up, the average decrease in the IOP was 17 mmHg (P < 0.001) after mitomycin C, 15 mmHg (P = 0.003) after GDD surgery, and 14.4 mmHg (P = 0.001) after CPC. There were no differences in the proportion of patients who developed postoperative IOP above 20 mmHg (P = 0.50) and in the proportion who developed hypotony (P = 0.10) among the three groups. Two grafts failed after mitomycin C and one failed after CPC. Among the three procedures, there were no differences in the proportion of patients who experienced either an improvement (P = 0.14) or a decrease (P = 0.22) in the visual acuity by more than one line after the glaucoma procedure. One patient each in the GDD group and the CPC group lost light perception after the procedure. The risk of graft failure was almost three times higher for each additional PKP (odds ratio = 2.80, P = 0.02). CONCLUSIONS No differences were found among the three glaucoma procedures with respect to controlling IOP and graft failure. There was a trend for patients treated with CPC to have a higher incidence of graft failure, glaucoma failure, hypotony, and visual loss by more than one line, although this was not statistically significant. The number of PKPs was associated with graft failure, independent of the surgical procedure.