We consider the general measurement scenario in which the ensemble average of an operator is determined via suitable data-processing of the outcomes of a quantum measurement described by a POVM. We determine the optimal processing that minimizes the statistical error of the estimation.A measurement in Quantum Mechanics is usually associated to an observable represented by a selfadjoint operator X on the Hilbert space H of the quantum system [1], with the eigenvalues x i defining the possible outcomes of the measurement. The probability distribution of the ith outcome is given by the Born ruleρ being the density operator of the state and P i denoting the orthogonal projectors in the spectral decomposition X = N i=1 x i P i (for the sake of illustration here we consider only finite spectrum). Consequently, the expected value for the outcome-averaging over repeated measurements is given by the ensemble average X = Tr[ρX], with statistical error proportional to the r.m.s.∆X 2 , with ∆X 2 := X 2 − X 2 .There are, however, more general kinds of measurements that can be performed in the lab, which are not necessarily associated to any observable, nevertheless enable the experimental determination of ensemble averages: these are the measurements that are described by POVM's. A POVM (acronym for Positive OperatorValued Measure) is a set of (generally nonorthogonal) positive operators P i 0, 1 i N which resolve the identity N i=1 P i = I similarly to the orthogonal projectors of an observable, whence with the same Born rule (1). This more general class of quantum measurements includes also the description of optimal joint measurements of non-commuting observables [2,3], along with the measurements of parameters with no corresponding observable such as the phase of a harmonic oscillator [4], and many other practical measurements such as optimized discrimination of states for quantum communications [5], and, most interesting, the so-called informationally complete measurements [6], i. e. measurements that allow to determine the density matrix of the state or any other desired ensemble average, as for the so-called Quantum Tomography [7]. Moreover POVM's also allow to provide a full description of the measurement apparatus, including noisy channels before detection [8]. The POVM's are not just a theoretical tool, since there is a general quantum calibration procedure in order to determine experimentally the POVM of a measurement device by using a reliable standard [9].How can we experimentally determine the ensemble average of the (generally complex) operator X using a POVM? Clearly this is possible if X can be expanded over the POVM elements (mathematically we denote this condition as X ∈ Span{P i } i=1,N . This means that there exists a set of coefficientsWhen S ≡ B(H) (i. e. when all operators can be expanded over the POVM), then the measurement is informationally complete. Obviously, once the expansion (2) is established one can obtain the ensemble average of X by the following averaging X =