This study evaluates the performance of an indirect injection (IDI) diesel engine fueled with cotton seed biodiesel while assessing the engine's multi-fuel capability. Millions of tons of cotton seeds are available in the south of the US every year and approximately 10% of oil contained in the seeds can be extracted and transesterified. An investigation of combustion, emissions, and efficiency was performed using mass ratios of 20-50% cotton seed biodiesel (CS20 and CS50) in ultra-low sulfur diesel #2 (ULSD#2). Each investigation was run at 2400 rpm with loads of 4.2 - 6.3 IMEP and compared to the reference fuel ULDS#2. The ignition delay ranged in a narrow interval of 0.8-0.97ms across the blends and the heat release rate showed comparable values and trends for all fuel blends. The maximum volume averaged cylinder temperature increased by approximately 100K with each increase in 1 bar IMEP load but the maximum remained constants across the blends. The gas to cylinder walls radiation and convection heat fluxes for both ULSD#2 and CS50 were 1.8 MW/m2 and 2.5MW/m2 respectively. The energy specific fuel consumption (ESFC) for CS50 was 4.4% less than ULSD#2 at 6.3 bar IMEP. The indicated thermal efficiency of the engine ranged from approximately 45-50% while the mechanical efficiency ranged from 70-80%. The nitrogen oxide (NOx) and soot showed minimum values with the CS20 fuel blend. Overall, the study confirmed that concentrations of up to 50% cotton seed biodiesel in ULSD are effective at maintaining performance and efficiency of a small bore IDI engine and the high tolerance of such an engine to biodiesel.