Purpose: Cardiac [I-123]metaiodobenzylguanidine scintigraphy (123I-MIBG), reflecting postganglionic cardiac autonomic denervation, is proposed for early detection of Parkinson's disease (PD; reduced tracer uptake) and separation from Multiple System Atrophy (MSA; preserved tracer uptake). However, several recent studies report on frequent unexpected 123I-MIBG results in PD and MSA. We sought to determine, whether 123I-MIBG is feasible to discriminate PD from MSA in unselected geriatric patients in clinical practice. Materials and Methods: We screened consecutive patients, that underwent 123I-MIBG for diagnostic reasons. Delayed 123I-MIBG uptake (heartimediastinum ratio; H/M ratio) was verified by clinical diagnosis of PD, MSA, and ET based on a two-stage clinical assessment: comprehensive baseline (including autonomic testing and additional neuroimaging) and confirmatory clinical follow-up. Results: 28 patients with clinical diagnosis of PD (N = 11), MSA (N = 9), and Essential Tremor (ET, N = 8) were identified. In one third (9/28) nuclear medical diagnosis deviated from clinically suspected syndrome. Visual interpretation of 123I-MIBG identified two cases (MSA and El) with indeed normal 123I-MIBG uptake. Detailed review of clinical phenotypes provided only in two cases (PD and ET) an adequate explanation (correction of initial diagnosis and confounding drug history) for unexpected 123I-MIBG. In conclusion, 123I-MIBG did not match initial clinical phenotype in 27% PD, 44% MSA, and 25% ET patients. Conclusion: 123I-MIBG scintigraphy is a known specific and valuable technique in scientific approaches and well-defined and highly selected samples. However, predictability of 123I-MIBG based nuclear medical diagnosis for individual cases and thus, feasibility in routine clinical practice is limited. Our clinical series emphasize clinical verification of 123I-MIBG results on an individual basis in clinical routine.