Objectives In this study, intravitreal injection of triamcinolone acetonide (TA) was compared with posterior subtenon injection of TA for treatment of diabetic macular edema (DME). Materials and Methods In this prospective, open, randomized, parallel group, comparative study, 60 patients of diabetic macular oedema visiting the Department of Ophthalmology, Govt. Medical College, Patiala were included. The patients fulfilling the inclusion criteria and having none of the exclusion criteria were enrolled in the study after obtaining written informed consent. Patients were then randomized into two groups (group I, II) and received intravitreal and posterior subtenon injection of triamcinolone acetonide, respectively. The comparison was based on change in best corrected visual acuity and macular thickness using optical coherence tomography (OCT). The results were subjected to statistical analysis and observations thus made in both groups were compared. Results With intravitreal TA, the mean pre-treatment CMT, mean post-treatment CMT and mean reduction in CMT were 395.53 ± 15.31 μm, 221.2 ± 10.71 μm and 174.33 μm (44.08%) while the mean pre-treatment VA, mean post-treatment VA and mean improvement in VA were 0.79 ± 0.16, 0.51 ± 0.15 and 0.28 (36.11%) logMAR units. With posterior subtenon TA, the mean pretreatment CMT, mean post-treatment CMT and mean reduction in CMT were 394.43 ± 15.03 μm, 247.3 ± 11.82 μm and 147.13 μm (37.3%) while the mean pre-treatment VA, mean post-treatment VA and mean improvement in VA were 0.81 ± 0.15, 0.58 ±0.14 and 0.23 (28.24%) logMAR units. The mean pre-treatment IOP, mean post-treatment IOP and mean rise in IOP with intravitreal TA were 16.67 ± 1.92 mm Hg, 18.87 ± 1.81 mm Hg and 2.2 mm Hg (13.19%), whereas with posterior subtenon TA were 16.87 ± 1.85 mm Hg, 17.4 ± 1.59 mm Hg and 0.53 (3.14%). Conclusions When used in diabetic macular edema, intravitreal triamcinolone acetonide is more effective than posterior subtenon triamcinolone acetonide in reducing the central macular thickness, although it produces a greater rise in IOP than PST.