The incidence of melanoma (MM) is among the fastest rising cancers in the western countries. Positron Emission Tomography with Computed Tomography (PET/CT) is a valuable non-invasive tool for the diagnosis and staging of patients with MM. However, research on the value of PET/CT in follow-up of melanoma patients is limited. This study assesses the diagnostic value of PET/CT for follow-up after melanoma surgery. This retrospective study includes patients with MM who performed at least one PET/CT scan after initial surgery and staging. PET/CT findings were compared to histology, MRI or fine needle aspiration (FNA) to estimate the diagnostic accuracy. The diagnostic performance of PET/CT performed in patients with and without a clinical suspicion of relapse was compared. 238 patients (526 scans) were included. Of the 526 scans 130 (25%) scans were PET-positive, 365 (69%) PET-negative, and 28 (5%) had equivocal findings. Sensitivity was 89% [0.82-0.94], specificity 92% [0.89-0.95], positive and negative predictive values of 78% [0.70-0.84] and 97% [0.94-0.98] respectively. When stratified for reason of referral there was no statistical significant difference in the diagnostic accuracy of PET/CT between patients referred with or without a clinical suspicion of relapse. This study demonstrates that PET/CT despite a moderate sensitivity has a high negative predictive value in the follow-up of melanoma patients. Thus, a negative PET/CT-scan essentially rules out relapse. However, the frequency of false positive findings is relatively high, especially among patients undergoing a "routine" PET/CT with no clinical suspicion of relapse, potentially causing anxiety and leading to further diagnostic procedures.