The effect of vehicle transmission type on driver injury severities have not been thoroughly studied. The study used four-year historical crash data that occurred between the year 2019 and 2022 in Ghana. The data shows 1856 and 2272 crashes for automatic and manual transmission, respectively. The study examined the factors influencing driver injury severity in crashes involving vehicles with manual and automatic transmissions, using Random Parameter Mixed Logit Model to account for heterogeneity in the dataset. It was observed that use of manual transmission is related to a higher risk of incapacitating and fatal injuries compared to automatic transmission. Specifically, for automatic transmission vehicle-involved crashes, factors related to fatal injury were overaged vehicles, public transport, morning and evening peak hours, head-on and rollover crashes. Crashes involving saloon cars and low age cars were associated with incapacitating injury whiles rainy weather condition was related to both fatal and incapacitant injuries. Regarding manual transmission, fatal injury was associated with crashes involving male and novice drivers, cars, pickup trucks, HGV, public transports, morning and evening peak hours, rainy weather conditions and curved roads. Also, buses, private cars and trip distance were related to incapacitating injury. The rollover crashes and overaged vehicles were also associated with both fatal and incapacitating injuries. Four random parameters demonstrated heterogeneity in means, with two factors influencing the variances of two parameters for automatic transmission model. For the manual transmission model, five random parameters showed heterogeneity in means, with four variables influencing the variances of three parameters. These findings are valuable for policymakers, manufacturers, and drivers in implementing targeted interventions and safety measures to promote road safety.