Analysis and simulation of biodiesel synthesis from neem (Azadirachta indica) oil and methyl acetate using immobilised lipase enzyme in semi-fluidised bed bioreactor has been performed in the present study. Versatile software package has been developed for the analysis of the performance characteristics of the semi-fluidised bed bioreactor. The reliability of the software has been tested and verified by comparing with experimental data compiled on laboratory scale as well as on pilot plant scale. The dependence of reactor performance on different system/operating parameters such as feed flow rate, molar ratio of neem (Azadirachta indica) oil to methyl acetate, particle size has been analyzed and illustrated graphically. The specific advantages of this bioreactor for biodiesel synthesis have also been highlighted. Comparison has also been made between the performance of the bioreactor under consideration and that of fully fluidised bed bioreactor. As compared to fluidised bed bioreactor, bioreactor of semi-fluidised configuration provides larger substrate conversion at larger feed flow rates but within a smaller reactor volume. An exclusive feature of this bioreactor is that unlike other industrial bioreactors, the fractional substrate conversion increases with increase in substrate flow rate. The operating cost of bioreactor of this kind shall however be higher.