The Plinian columns formed during the magmatic phase of the A.D. 79 eruption of Vesuvius alternated several times between fully stable, buoyantly rising regimes and unstable regimes of partial or total collapse. Six pyroclastic density currents (PDCs) were produced during unstable regimes, and ultimately caused the destruction of Roman towns around the volcano. Through new measurements of juvenile clast density and estimations of ascent parameters, we show that four partial collapses were likely triggered by increases in the abundance of dense juvenile clasts within the eruptive column. In contrast, the total collapse probably occurred in response to an increase in the wall-rock content injected into the plume during a progressive widening of the conduit. A sixth low-energy, small collapse resulted from high abundances in both dense juvenile clasts and wall-rock material. Simulations of eruption column behavior already account for the effects of variations in conduit radius, mass discharge rate, and particle size, but have yet to include variable clast density and wall-rock abundance that cause temporal variations in plume density. Our results suggest that both parameters can exert a significant control on the potential for generation of PDCs.