Sampras, the world No 2 who was back on court for the first time since he was forced to retire from last month's Monte Carlo Open with an ankle injury, had to fight to find a way past the Spanish clay-court specialist Carlos Costa in a 6-3, 7-5 victory.
By contrast, Agassi, the world No 1, cruised to a 6-2, 7-6 win over the German Marc Goellner in just 74 minutes in a one-sided match played in some of the coldest conditions on the ATP Tour so far this year.
Sampras and Costa shared dramatic long rallies in their entertaining clash. The American needed luck to gain a crucial service break to lead 5-3 in the first set when a Costa volley at the net hit the net cord and bounced back on the Spaniard's side.
Sampras had to produce two big serves to save break points in the next game before serving out for the first set after 43 minutes and going on to take the second 7-5 after a fight in the sunshine.
Agassi, however, was rarely tested by Goellner in their earlier match, played in overcast conditions.
Wearing black socks and black shoes, creating the impression of walking boots from a distance, Agassi had the appearance of a hiker heading off for a morning in the hills with his shirt hanging scruffily over his long baggy shorts.
In Rome, Mary Pierce removed any lingering doubts over her fitness with a 6-1, 6-2 win over Canada's Sonya Jeyaseelan in the second round of the Italian Open on Wednesday. The Australian Open champion, playing her first match since pulling out of last week's tournament in Hamburg with a kidney infection, won in just under a hour with a ruthless display of fierce groundstrokes.Reuse content