Both oral and intraocular routes have been recommended for medication administration in toxoplasmic retinochoroiditis; however, available data, in support or against, are scarce. The objective of this study was to compare the efficacy of intravitreal clindamycin plus dexamethasone (IVCD) and conventional oral therapy (COT) including pyrimethamine, sulfadiazine, folinic acid and prednisone in active toxoplasmic retinochoroiditis. In this prospective randomized single-blind clinical trial, patients with active toxoplasmic retinochoroiditis received either IVCD (n = 32), or COT (n = 34) for 6 weeks. Changes of best-corrected visual acuity, retinal lesion size, and vitreous inflammation before and after treatment, as well as complications/side-effects and recurrence rate within at least 2 years of follow-up were compared between groups. Although all the variables improved significantly at 6 weeks within each group, changes were comparable between the IVCD and COT receivers. There was only one case with hepatotoxicity in the COT group which responded favorably to drug change. No injection-related complication was observed. Recurrence rates were 12.5 and 14.7 % in the IVCD and COT groups, respectively (p = 0.54). In conclusion, both IVCD and COT are equally effective against active toxoplasmic retinochoroiditis but the former is apparently safer and more convenient.