The researchers followed more than 8,700 men who had low levels of the hormone, of whom 1,223 took a testosterone supplement for a median period of around two years.
Three years later, nearly one in five of the men who had not taken a supplement had suffered a heart attack or stroke, or had died.
That figure jumped to one in four among the group who had been treated with testosterone -- an overall increased risk of nearly 30 percent.
The increased risk of catastrophic events was especially notable, said researcher Anne Cappola of the University of Pennsylvania, because "the men who were taking testosterone in this study were slightly healthier to begin with."
The men receiving testosterone also tended to be younger -- they had an average age of 61, compared to an average age of 64 for the untreated men.
"These findings raise concerns about the potential safety of testosterone therapy," the authors, including lead researcher Rebecca Vigan of the University of Texas, wrote in the study, published in the Journal of the American Medical Association.
They said further studies were needed "to properly characterize the potential risks," especially among older men or men with other risk factors.
The number of annual prescriptions for testosterone therapy increased five-fold between 2000 and 2011 in the United States, reaching 5.3 million prescriptions worth about $1.6 billion, the authors emphasized.
The therapy is recommended for those with below-normal levels of the hormone whose symptoms include diminished sex drive, low energy, and worsening memory.
In addition to improving sex drive and bone density, the hormone has been shown to increase muscle mass and strength.
It is not clear from this research whether the increased risk of death, heart attack and stroke existed among patients prescribed testosterone therapy for "low T syndrome" or younger men taking it for physical enhancement, Cappola said.
An ongoing randomized trial of more than 800 men over the age of 65 receiving testosterone or a placebo could help provide guidance for older men considering testosterone therapy.
Until more is known, however, "prescribers and patients should be wary," she said.