A set of 19 silicon-bridged C-2-symmetric zirconocenes rac-R'Si-2(2-Me-4-R-indenyl)(2)ZrCl2 of varying steric demand in position 4 were synthesized and screened in propene homopolymerization in a high-throughput experimental setup. The size and accuracy of the experimental data set allow to identify surprisingly good correlations among stereoselectivity, regioselectivity, and molecular weight capability (R-2 approximate to 0.8-0.9) over a broad range. We rationalize this trend by assuming that steric tuning in the 4-position affects both preferred insertion and stereoerror formation similarly but leaves other barriers largely unaffected. A quantitative structure-activity relationship based on one single computational descriptor, Delta%V-Bur -using the difference in the percent of buried volume between the "blocked" and "open" quadrants of the catalyst precursor-is established. Provided that a large sphere of 5.0 angstrom is used, stereoselectivity can be predicted with unprecedented accuracy, i.e., a mean average deviation (MAD) of 0.18 kcal/mol (Delta Delta Gt(enantio)), 0.0007 (sigma, probability that the preferred propene enantioface is selected at an active site of given chirality), or 0.3% (mmmm pentads). On the basis of this empirical model, we predicted that the catalyst with R = o-tolyl is an ideal candidate for high stereoselectivity/high MW capability. Ad hoc synthesis and testing of the precursor confirmed the expectations: the catalyst shows the highest stereoselectivity reported so far (sigma= 0.9999) for metallocenes at 60 degrees C, while maintaining a high MW capability (M-w > 1 MDa) and relatively high regioselectivity.