The aerosol first indirect effect (FIE) is typically characterized by a reduction in cloud droplet size and an increase in cloud optical thickness in the presence of high concentrations of condensation nuclei. Past studies have derived observational evidence of the FIE in specific locations and conditions, yet critical uncertainties in the validity of this conceptual model as it applies to a range of cloud types and meteorological settings remain unaddressed. We utilize five years of surface aerosol measurements and Moderate Resolution Imaging Spectroradiometer (MODIS) observations of cloud properties to discern the FIE in springtime cloud statistics over the Southern Great Plains region of the United States. We extend this analysis to explore the role of three confounding factors: cloud phase, observational uncertainty and the role of regional meridional flow. While high aerosol days are dominated by smaller average droplet size in liquid clouds, the response of cloud optical thickness is variable and is dominantly a function of cloud water path. Ice clouds experience more variability in their response to high aerosol loading and satellite retrieval uncertainty thresholds. Finally, the direction of meridional flow does not play a large role in stratifying the cloud response to different aerosol loading. Overall, these observations show that much of the classical theory for liquid clouds is supported. Higher aerosol loadings are correlated with a reduction in effective radius and generally higher cloud optical thickness, and this relationship dominates over any driving influence from the low-level jet. However, for ice clouds we see a variable response that may be driven by aerosol composition and cold cloud microphysics. These observations provide further insight into the importance of considering deviations from the classic FIE in understanding regional variability in aerosol-cloud interactions in a continental setting.