A staple cartridge is disclosed. The staple cartridge can include a cartridge body having a plurality of staple cavities defined therein. The staple cavities can be obliquely oriented relative to a longitudinal axis of the staple cartridge. The staple cavities can be arranged in a plurality of rows including an inner row, an intermediate row, and an outer row. The lateral and/or longitudinal spacing and/or overlap between the staples in adjacent rows can vary to optimize the flexibility and/or sealing properties of the staple line. The size and orientation of the staples can also vary row-to-row and/or longitudinally.