The effect of annealing on the structure and superconductivity of Bi 2Sr 2CaCu 2O 8+ δ has been investigated on high-quality and large single crystals grown by the traveling solvent floating zone technique. Vacuum annealing was carried out on crystals sealed in quartz ampoules under different oxygen pressure ranging from 8×10 −1 to 5×10 −4 bar. The as-grown and post-annealed crystals were explored by induction-coupled plasma atomic emission spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM) and magnetization measurements. It was demonstrated that the oxygen homogeneity of the as-grown crystals has a direct influence on the post-annealed samples. The superconducting transition temperature, T c was found to be affected more strongly by the annealing oxygen partial pressures, p(O 2), than by the annealing temperature. T c decreases considerably from 92 to 29 K with decreasing p(O 2) from 1 down to 4×10 −2 bar, however, increases surprisingly to 62 K with further decreasing p(O 2) to 5×10 −4 bar. The transitions remain relatively sharp for the samples annealed under p(O 2)=8×10 −1–4×10 −2 bar, with no evidence of significant structural change by powder XRD measurement. XRD studies indicate that the crystals have orthorhombic symmetry. The refinement result for XRD data shows that the c-axis expands, while both a- and b-axis contract slightly with decreasing p(O 2). The relation between T c and the c-axis lattice parameter suggests that the change of T c is correlated with a redistribution of holes between the Bi–O layers and the Cu–O planes. Impurity phases were found to segregate from samples annealed under p(O 2) < 4×10 −2 bar. The one-dimensional incommensurate superstructure along the b-axis was observed by TEM in the crystal annealed at p(O 2)=1×10 −3 bar. The lattice strain caused by the high-vacuum annealing possibly affect the Cu–O–Cu angle and lead to an anomalous change in T c.