The lava domes of the Cixerri half-graben (SW Sardinia) are part of the subduction-related igneous activity that developed in Sardinia during the Upper Eocene-Middle Miocene (38–12 Ma), with calcalkaline and high-K calcalkaline affinity. The investigated rocks are porphyritic basaltic andesites and andesites, with amphibole, plagioclase and minor clinopyroxene phenocrysts included in a groundmass composed of the same phases together with feldspar, quartz and opaque oxides. 40Ar/39Ar analyses of plagioclase and amphibole separates from an andesite indicate a crystallization age of 21.31 ± 0.05 Ma. The high abundance of amphibole in the Cixerri rocks, unlike andesites from the neighboring Sardinian districts, could be explained with the high calculated oxygen fugacity (NNO+1–NNO+2) and H2O content (up to 9 wt%) in the Cixerri magmas. Bulk-rock major and trace element variations, and mass balance calculations are consistent with a magma evolution mainly driven by fractional crystallization of amphibole and plagioclase, which occurred in a polybaric plumbing system, as highlighted by the calculated pressure of amphibole crystallization (2–4 kbar and 6–9 kbar). Bulk rock isotope variations (87Sr/86Sri = 0.70701–0.70786 and 143Nd/144Ndi = 0.512328–0.512436) indicate that the magma evolution took place in open-system conditions with a low degree of crustal assimilation. The HREE flat patterns point to a magma source in the spinel stability field located in a mantle wedge depleted in incompatible elements and metasomatized by slab and sediment derived fluids and melts.