The addition of small amounts of B to Ti–6Al–4V alloy reduces the as-cast grain size by an order of magnitude and introduces TiB phase into the microstructure. The effects of these microstructural modifications on both the high cycle fatigue and cyclic stress–strain response were investigated. Experimental results show that B addition markedly enhances the fatigue strength of the alloy; however, the influence of prior- β grain size was found to be only marginal. The presence of TiB particles in the matrix appears to be beneficial with the addition of 0.55 wt.% B to Ti–6Al–4V enhancing the fatigue strength by more than 50%. Strain-controlled fatigue experiments reveal softening in the cyclic stress–strain response, which increases with the B content in the alloy. Transmission electron microscopy of the fatigued specimens indicates that generation of dislocations during cyclic loading and creation of twins due to strain incompatibility between the matrix and the TiB phase are possible reasons for the observed softening.