There have been few studies to date describing fatigue-crack propagation thresholds under mixed-mode loading conditions in the presence of cracks, that are small as compared to the characteristic microstructural dimensions. To address this need, the variation in mixed-mode, high-cycle fatigue-crack growth thresholds with crack size is reported for a Ti-6Al-4V turbine blade alloy with a fine-grained bimodal microstructure. Specifically, threshold behavior is examined for large through-thickness cracks >4 mm in length), short through-thickness cracks (~200 μm in length), and microstructurally-small surface cracks (10–50 μm in diameter) under combined mode I and mode II loading at load ratios (ratio of minimum to maximum load) ranging from 0.1 to 0.8. For mode-mixities ranging from pure mode I to predominantly mode II, large crack, mode I Δ K I,TH thresholds were found to decrease substantially with increasing phase angle. However, by characterizing in terms of the range in strain energy release rate, Δ G TH, incorporating both mode I and mode II contributions, it was observed that the pure mode I threshold could be regarded as a ‘worst case’ under mixed-mode loading in this alloy. By estimating the effective crack-driving force actually experienced at the crack tip, the observed increase in the mixed-mode Δ G TH threshold with mode-mixity was attributed to an increasing influence of crack-tip shielding due to crack closure and crack-surface interference. Equivalent thresholds for through-thickness short cracks, where the crack wake and hence the effect of such shielding is minimized, were consequently far less sensitive to mode-mixity and corresponded in magnitude to the shielding-corrected large-crack thresholds. This effect was accentuated for the measured thresholds of microstructurally-small surface cracks; such small-crack, mixed-mode Δ G TH thresholds not only displayed a minimal influence of mode-mixity but were up to two orders of magnitude smaller than those for corresponding large cracks at the same load ratio and mode-mixity conditions.