First, a reality check: Only about 1% of tax returns get flagged by the IRS.
Those who have particularly high-income—especially if it comes from many different sources—and who take lots of deductions, have far higher odds for an audit since the IRS is most likely to flag returns that are out of the norm.
Be aware that write-offs that are considerably higher than the norm may also trigger an audit, even if your income is not in the Bill Gates territory. So, if you make large charitable deductions, be sure you have receipts and, in the case of donated items, appraisals. Claiming huge deductions for business travel and entertainment can be a red flag if the amount is disproportionately high relative to your income; ditto for claiming, say, 100% business use for your car. Make sure you have receipts and proof that these expenses were in fact related to business—a calendar showing meetings and mileage log for your car, for example.
Also keep in mind that an average Joe can sometimes get tripped up by a data-entry error. So make sure you fill in all your information correctly and be sure to include all pertinent information (like those miscellaneous 1099 forms). When you’re done double-check your work.