PURPOSE: The purpose of this study is to evaluate the efficacy of (18)F-FDG-PET as first-line diagnostic investigation, prior to performing a direct laryngoscopy with biopsy under general anesthesia, in patients suspected of recurrent laryngeal carcinoma after radiotherapy. PATIENTS AND METHODS: 150 patients suspected of recurrent T2-4 laryngeal carcinoma at least two months after prior (chemo)radiotherapy with curative intent for resectable disease were randomized to direct laryngoscopy (CWU: conventional workup strategy) or to (18)F-FDG-PET only followed by direct laryngoscopy if PET was assessed 'positive' or 'equivocal' (PWU: PET based workup strategy), to compare the effectiveness of these strategies. Primary endpoint was the number of indications for direct laryngoscopies classified as unnecessary based on absence of recurrence, both on direct laryngoscopy and on six month follow up. Safety endpoints comprised resectability of recurrent lesions and completeness of surgical margins following salvage laryngectomy. RESULTS: Intention-to-treat analyses were performed on all randomized patients (CWU: n=74, PWU: n=76). Tumor recurrence was similar in both groups: 45 patients (30%; 21 CWU, 24 PWU) within six months. In 53 patients in the CWU arm (72%, 95% CI: 60-81) unnecessary direct laryngoscopies were performed compared to 22 in the PWU arm (29%, 95% CI: 19-40) (p