Gaming controllers are input devices that provide a tangible or intangible interfaces for the gamers to interact with the videogame. Regardless of age and gender, those controllers are increasing in demand in the growing market of the videogame industry. Manufacturers have created a wide range of controllers, but those are not equally suitable for every user population due to the shortcomings of the controllers, including challenging operations and anthropometric and biomechanical incompatibility that ultimately leads to an increase in physical and mental demand. While the design of the controllers is greatly influenced by the buttons/switches and joystick configurations, it can be very difficult for players, especially inexperienced ones, to determine which game controller is best for them. Therefore, the goal of this study is to identify the best gaming controller configuration for improved user performance. A comparative usability study was conducted with three different gaming control interfaces with the participation of the 20–40 age range of the student population. The testing methods included anthropometric and biomechanical compatibility study with the controllers considering the hand anthropometry and total range of motion data (5th, 50th, and 95th percentile data) respectively. Materials included the NASA-TLX to compare the perceived workload by the users, the System Usability Scale (SUS) to evaluate the ease of use, and heuristic evaluation to identify usability issues with three controllers. The results indicated that the anthropometric and biomechanical compatibility were reasonable with the selected controllers. The NASA-TLX and SUS scores showed variation in mean value with no significant difference after performing one-way ANOVA. Through heuristic evaluation, a wide range of usability issues have been identified. A total of 40 issues were listed for console 1, console 2, and console 3. Future study indicates the incorporation of more participants to strengthen the validity of the results obtained.