A new class of mixing rules, with van der Waals one-fluid mixing rule and second venal coefficient constraints, was developed for cubic equations of state (EOS) for application to various asymmetric, highly nonideal chemical systems. This approach evolved from previous research in the EOS field. The resulting mixing rule is practical in application, yet more flexible than Huron-Vidal or Wong-Sandler mixing rules and depends only on composition and temperature. It also avoids the problems associated with the Wong-Sandler mixing rules. A cubic EOS with the new mixing rules was applied successfully to complex mixtures. The new rules reduce to van der Waals mixing rules when the parameters in the nonrandom excess Helmholtz free energy are set to zero. Since many times the classic miring relies worked very well for nonpolar systems, it is extremely desirable that the composition-dependent mixing rules reduce to the classic mixing rules. Preserving this capability also ensures that the binary interaction parameters for the classic quadratic mixing rules in the DECHEMA Chemistry Data Series for mixtures of low boiling substances and other existing databases for systems involving hydrocarbons and gases can be used directly in the new EOS mixing rules, in addition to liquid-activity coefficient model parameters currently reported in the Series.