Propose: To report two cases of severe acute multi-systemic failure with bilateral ocular toxoplasmosis in immunocompetent patients from urban settings in Colombia.Observations: We report two immunocompetent male patients aged 44- and 67-years-old who, despite not having visited the Amazonian region in Colombia, had severe bilateral posterior uveitis and extensive-bilateral macular lesions and multiple organ failure that required admission to an intensive care unit. was positive by PCR assay in vitreous humor samples. Patients were treated with intravitreal clindamycin and dexamethasone in addition to systemic treatment with trimethoprim-sulfamethoxazole. In both patients, infection by atypical strains was confirmed; in one case by serotyping and in another one by genotyping (ROP 18 virulent allele). After 2 and 4 months of treatment respectively, the patients showed improvement of the posterior uveitis and its systemic manifestations. However, there was no significant visual acuity improvement due to bilateral extensive macular involvement.Conclusions And Importance: Clinicians should be aware that toxoplasmosis originating from South America could be associated with severe acute multisystemic and intraocular bilateral involvement, even in patients with no history of exposure to jungle environments.