OBJECTIVES: The burden of childhood injury is huge especially in children less than five years, yet little has been done in estimating the economic cost of injury in children of this age bracket. Evidence on economic cost injury among children could inform policy in the design and implementation of safety and prevention interventions. This study sought to estimate the household cost and assess the burden of injury in children less than five years on household in an urban setting in Ghana. METHODS: A multistage sampling was used to select 600 households in Ejisu in the Ejisu-Juabeng Municipality of Ashanti Region. Structured questionnaire was used in the data collection. The data were analysed into descriptive statistics in STATA version 13.0 to estimate the direct, indirect and total cost of injury. Sensitivity analysis was run on the cost estimates for a period of 5-10 years RESULTS: The educational level 2.2[95% CI: 1.6, 3.0], living room 0.6 [95% CI:0.4, 0.7]) and household size 0.7[95% CI: 0.6, 0.9] were statistically significant risk factors of injury in children under five years. The total sum of GHC 3,922.60 (US$ 1,028.20) averaging GHC6.67 (US$ 1.83) was incurred on injury per household. An indirect cost of over four million Ghana Cedis (GHC4, 808,938) US$ 1,260,534.81 was lost averaging GHC814.89 (US$ 213.60) per household. The time value lost was 10,690 cumulative working days with a monetary equivalence of GHC 4,754,320 (US$1,246,217.56) averaging GHC17, 873 (US$ 4,684.92) per household.  The burden was in the form of amputation being 24.2%, and visual disabilities 8.3%. Physical and educational developments of the children were also affected. CONCLUSIONS: The study revealed high household cost and varying burden of injury in children under five years. The findings are significant for policy update, design and implementation of safety and preventive interventions for injury control.