To report outcomes of tacrolimus immunosuppression after penetrating keratoplasty (PK) in very young children. Retrospective, consecutive, cohort study of children undergoing PK at a tertiary children's hospital between 2005 and 2016. Oral tacrolimus immunosuppression was given for 2 years, followed by topical tacrolimus. Fourteen children (20 eyes) had 24 PKs; nineteen eyes had primary PKs, five eyes had repeat PKs. Mean age at primary graft was 95 days (3.1 months) for anterior segment dysgenesis (ASD), 430 days (14.3 months) for non-ASD children. Eleven children (15 eyes) had ASD. Three children (five eyes) had non-ASD: two children (three eyes) had glaucoma-related corneal opacity and one child (two eyes) had congenital hereditary endothelial dystrophy (CHED). One-year rejection-free survival rates following primary PK was 80% for ASD (n = 15) and 100% for non-ASD (n = 4). At final review, 5/15 of primary grafts for ASD were clear. 10/15 failed after a mean of 19 months, specifically attributable to infection (n = 2), rejection (n = 2) and glaucoma (n = 2). 4/4 primary non-ASD grafts are clear at final review (mean follow-up = 77 months). All repeat grafts (n = 5), failed after a mean of 38.25 months. Considering all grafts, 15/24 (62.5%) failed: 5/15 due to infection, 2/15 due to rejection, 8/15 due to glaucoma, phthisis, perforation or vascularised with no rejection. At last review (mean = 58.1 months, range 28-84), overall cohort survival is 37.5%. Final visual acuities range between 0.86 and 2.4 LogMAR. We compare our results to published literature: 1-year graft survival was higher than previously reported, with lower failure due to rejection. Overall infection rates did not increase, however, proportionally, severe infections were higher. Overall graft survival is at least comparable to reported literature.