In March 1996 Maryland hired Angelos to represent the state in its suit against tobacco companies with a 25% contingency fee. After Angelos filed suit on behalf of the state the trial court ruled that the state's recovery would be limited to subrogation of losses through programs such as Medicaid; this would have effectively ended the state's case. Angelos successfully lobbied the state legislature to change the law to allow the state's suit to proceed. The state legislature also cut Angelos' fee to 12.5%. Eventually he settled for $150 million paid over five years.
Angelos also represented the state of Maryland in a suit against Philip Morris and suing Wyeth, the makers of part of the diet pill combination fen-phen. As of 2019, Angelos's law firm currently had offices in Baltimore, Towson, and Cumberland, Maryland; Philadelphia, Bethlehem, and Harrisburg, Pennsylvania; and Knoxville, Tennessee. The firm is headquartered in the historic One Charles Center building in downtown Baltimore which was purchased by Angelos for $6 million in 1996.