His doctoral thesis, entitled Probabilistic Study of Structural Safety, was supervised by Charles E. Massonnet [de] and J. Ferry-Borges [pt].

In March 1983 he joined the faculty of the University of Colorado at Boulder as an associate professor in the Department of Civil, Environmental and Architectural Engineering.

His work has been funded by NSF, FHWA, ONR, NASA, USACE, AFOSR, ARDEC, NCHRP, US DOT UTC, CDOT, FDOT, PennDOT, ASCE, NATO, and by numerous other agencies including Pennsylvania Infrastructure Technology Alliance, ArcelorMittal, Modjeski and Masters, Progeny Systems Corporation, Henry Luce Foundation, U.K. Highway Agency and the Dutch Ministry of Infrastructure and Environment.

In 2012, Frangopol was described by ASCE as "a preeminent authority in bridge safety and maintenance management, structural systems reliability, and life-cycle engineering.

"[4] and in 2020, "Frangopol's groundbreaking research into infrastructure from a holistic perspective has earned him a reputation in the civil engineering community" as the "Father of Life-Cycle Analysis.