This study investigates the effects of critical operational and strategical decisions in order-picking warehouses on order pickers’ tour lengths. For this study, one of the most-commonly applied layouts in practice, called two-block layout with a central cross aisle, was considered. A full factorial experimental design and multiple-comparisons (Bonferroni t-tests) were applied to statistically determine the significance of various levels of storage policies, pick-list sizes, warehouse shape ratios, warehouse sizes and their all interactions on average tour length. The analysis showed that deeper storage areas were superior to wider areas in small- and medium-sized warehouses. Warehouse designs with a 1:1 width-to-depth shape ratio offered the most robust layouts. Within-storage aisle policy significantly reduced order-picking tour length and generally outperformed other storage policies.