A combined computational and experimental study was carried out to evaluate control of the microstructure of isotactic polypropene by C2‐symmetric zirconocenes with rac‐SiMe2[Ind]2‐based ligands. Building on the highly regio‐ and stereospecific catalyst combining 2‐Me and 4‐Ph substituents, we made further modifications to the ligand framework by systematic addition of alkyl substituents. Propene insertion barriers are given for a total of 24 catalysts. Calculations and experiments show that the series of catalysts produce highly stereoregular isotactic polypropene. Regiocontrol can be markedly improved by addition of 3‐Me substituents or by replacing 2‐Me with bulkier 2‐alkyl substituents on the indenyl ligand, but the former is accompanied by loss of stereocontrol and the latter by significantly increased overall barriers for propene insertion. The combination of methyl substituents and tBu groups on the 4‐Ph ligand substituents is shown to provide improved regiocontrol without sacrificing high stereocontrol.