Guardino won raves on Broadway and in feature character roles before establishing himself as a TV lead in the early 1960s. Craggy-faced, sporting bushy eyebrows, and often somewhat rumpled, he convinces as Italian-American tough guys in and out of uniform and on both sides of the law. TV generally cast Guardino in positions of responsibility including lawyers (DA Hamilton Burger on "The New Adventures of Perry Mason" CBS, 1973-74), G-men ("Monty Nash" syndicated 1971), and police brass in a series of pilots both successful and busted ("The Police Story" NBC, 1973; "Get Christie Love!" ABC, 1974). His TV credits include numerous guest shots and several miniseries including the Melvin Van Peebles-scripted "The Sophisticated Gents" (NBC, 1981) and the Las Vegas-set crime drama "The Neon Empire" (Showtime, 1989).
Guardino entered films with character turns in low-budget genre programmers before gaining kudos for a supporting role in the light Cary Grant-Sophia Loren vehicle "Houseboat" (1958) as a comically wolfish handyman. Guardino was part of the sturdy ensemble supporting CO Gregory Peck in the tough-minded Korean War drama "Pork Chop Hill" (1959) and Steve McQueen in the fine WWII actioner "Hell Is For Heroes" (1962). He made strong impressions as a brutish muscular Barrabas in "King of Kings" (1961) and as the former Marine husband of Anne Meara in "Lovers and Other Strangers" (1970). Guardino's many Broadway credits include starring opposite Lauren Bacall in the hit musical "Woman of the Year" (1981).