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18 F-fluciclovine PET is approved for prostate cancer recurrence imaging. According to the radiopharmaceutical package insert, only 3% of the tracer is expected to be excreted in the urine over the first 4 h. Yet, in clinical practice we noticed a higher percentage of bladder excretion. We sought to evaluate and quantify early 18 F-fluciclovine bladder radioactivity and determine whether refraining from voiding before 18 F-fluciclovine injection would mitigate it. Methods: In total, 159 patients underwent 18 F-fluciclovine PET/CT imaging as part of their clinical workup. The first 36 patients were instructed to void just before 18 F-fluciclovine injection; the subsequent 123 patients were not asked to void. The SUV max and SUV mean of the bladder, aorta, marrow, liver, and bladder volumes were determined. Comparing SUV mean of bladder to background, we characterized bladder radioactivity as insignificant (bladder , aorta), mild (bladder . aorta , marrow), moderate (bladder . marrow , liver), or intense (bladder . liver). Differences between the protocols were investigated. Results: Overall, 22% (35/159) of patients had moderate bladder activity and 8.8% (14/159) had intense bladder activity. A negative association was found between bladder volume and SUV mean . A significant difference was found between the voiding and nonvoiding groups, with 38.9% (14/36) versus 17.1% (21/123) of patients, respectively, having moderate bladder activity and 22.2% (8/36) versus 4.9% (6/123) of patients, respectively, having intense bladder activity. Conclusion: Refraining from voiding before 18 F-fluciclovine injection results in significantly lower urinary bladder radioactivity than does purposeful voiding before injection. We have modified our practice accordingly, particularly as moderate and intense bladder activity may mask or mimic local prostate cancer recurrence. Mechanisms underlying this phenomenon should be further investigated.