Thin film combinatorial sputter-deposited ternary Pt–Cr–V, Pt–Co–Cr, and quaternary Pt–Co–Cr–V catalysts for methanol electro-oxidation in direct methanol fuel cell were studied. Several compositions exhibited better MOR activities than pure Pt based on the peak current density and onset potential of the methanol oxidation reaction measured by voltammetry. Alloying 43% vanadium with pure platinum gave higher electrocatalytic activity evidenced by 5.9 times greater peak current density. Pt 30 Co 40 Cr 30 outperformed pure Pt by 12× in a ternary Pt–Co–Cr library. Alloying of vanadium into optimum PtCoCr compositions further improved methanoloxidation kinetics. Pt 25 Co 25 Cr 25 V 25 showed the highest catalytic activity with a peak methanol oxidation current density that was 17× higher than pure Pt and 1.5× higher than Pt 33 Co 33 Cr 33 . Atomic absorption studies of dissolved species in the electrolyte showed Co and Cr dissolution at higher rates than V, showing that the chemical ratio of Cr:Co:V in Pt 25 Co 25 Cr 25 V 25 changed to 0.738:0.862:1.000 after voltammetry. XPS analysis of Pt 25 Co 25 Cr 25 V 25 revealed a Pt-rich PtV binary compositional surface (Pt:V=89.04%:10.96%) formed after electrochemical testing. The active catalytic performance and good stabilities of catalysts in the PtCoCrV system suggest them as promising alternatives to Pt–Ru for methanol oxidation.