- We investigate the effect of event-by-event fluctuations of the fireball created in high energy nuclear collisions on hard probe observables. We show that spatial inhomogeneities lead to changes in the nuclear suppression factor of high momentum hadrons which can be absorbed in the quenching strength q. This can increase the theoretical uncertainty on extracted values of q by up to 50%. We also investigate effects on azimuthal asymmetries v2 and dihadron correlation functions. The latter show a promising residual signal of event-by-event quenching that might allow us to estimate the size of spatial inhomogeneities in the fireball from experimental data. 2011 Elsevier B.V.