© 2016, Copyright © Taylor & Francis Group, LLC. This article investigates the choice of working covariance structures in the analysis of spatially correlated observations motivated by cardiac imaging data. Through Monte Carlo simulations, we found that the choice of covariance structure affects the efficiency of the estimator and power of the test. Choosing the popular unstructured working covariance structure results in an over-inflated Type I error possibly due to a sample size not large enough relative to the number of parameters being estimated. With regard to model fit indices, Bayesian Information Criterion outperforms Akaike Information Criterion in choosing the correct covariance structure used to generate data.