LaHood's signature effort during the past four years has been to raise public awareness of the dangers of distracted driving.
He used his DOT pulpit to push for legislation, rules and behavioral changes that reduce the risks associated with driver distraction.
His commitment was instrumental in the Federal Motor Carrier Safety Administration's ban on texting and hand-held cell phones for truck drivers.
"On [LaHood's] watch highway fatalities have dropped by about 5,000 deaths per year," said John Horsley, executive director of the American Association of State Highway and Transportation Officials, in a statement.
"Distracted driving is a national priority today because of his personal zeal."
LaHood also participated in passage of the 2012 highway law, Moving Ahead for Progress in the 21st Century, which prescribes important reforms in the federal transportation program.
And he administered distribution of the $48 billion in transportation funding under the American Recovery and Investment Act of 2009.
Trucking interests had issues with some of DOT's decisions during LaHood's tenure.
The industry was not happy about DOT's 2009 deal on the hours-of-service rule.
In an attempt to break the legal logjam over the rule, DOT said that if the safety advocates who opposed the rule would suspend their suit, DOT would agree to draft a new rule.
American Trucking Associations liked the old rule and is not happy with the revised version.
And the legal battle continues, with both ATA and safety advocates contesting the revised rule.
LaHood was successful in negotiating a deal between the U.S. and Mexico over the contentious issue of cross-border trucking.
In the deal, Mexico agreed to suspend tariffs it had imposed in retaliation for the U.S. closing the border to long-distance carriage, while DOT set up a pilot program that permits a limited number of Mexican carriers to provide the service.
While ATA supported the deal, other trucking groups, including the Owner-Operator Independent Drivers Association and the Teamsters union, are in court against it.
LaHood, 67, served seven terms in Congress as a Republican from Illinois before President Obama tapped him for DOT. He was the second Republican Obama named, after former Defense Secretary Robert Gates.
In his farewell letter to DOT employees, he said, "This is the best job Ive ever had."
There is no word yet on LaHood's successor. The speculation for possible nominees has included Los Angeles Mayor Antonio Villaraigosa, former Pennsylvania Gov. Ed Rendell, retiring Rep. Steve LaTourette, R-Ohio, and former Rep. James Oberstar, D-Minn.