Vignale is known for his contributions to density functional theory. In 1987 he formulated, in collaboration with Mark Rasolt, the current density functional theory for electronic systems in the presence of a static magnetic field.  In 1996 he developed, with Walter Kohn (Nobel Laureate in Chemistry, 1998), the time-dependent current density functional theory for electronic systems subjected to time-dependent electromagnetic fields.  He is also known for his contributions to spintronics: in 2000, with Irene DAmico, he introduced the concept of spin Coulomb drag  (experimentally observed in 2005).  In 2003 he proposed, with Michael E. Flatte of the University of Iowa, the theoretical concept for a unipolar spin diode and a unipolar spin transistor.
Vignale is co-author (with Gabriele F. Giuliani) of a monograph on the quantum electron liquid, which is used by students and researchers for reference and self-study.  In 2011 he published a non-technical book "The Beautiful Invisible - Creativity, imagination, and theoretical physics", which presents theoretical physics as a form of art.  In the introduction to this book he writes  “A good scientific theory is like a symbolic tale, an allegory of reality. Its characters are abstractions that may not exist in reality; yet they give us a way of thinking more deeply about reality. Like a fine work of art, the theory creates its own world: it transforms reality into something else – an illusion perhaps, but an illusion that has more value than the literal fact.”