Purpose <p>To assess the clinical performance of [¹⁸F]piflufolastat PET/CT acquired on a total-body 194-cm LAFOV PET/CT system in patients with prostate cancer, with particular focus on detection rate, site-specific disease distribution, and the association between PET findings and serum PSA levels.</p> Methods <p>This retrospective single-centre study included 103 consecutive patients with prostate cancer who underwent clinically indicated [¹⁸F]piflufolastat PET/CT on 194-cm LAFOV PET/CT. Indications were primary staging (<i>n</i> = 42) or suspected recurrence (<i>n</i> = 61). Only the 8-min acquisition dataset was analyzed. PET findings were assessed on a patient basis and across predefined anatomical sites. In the recurrence subgroup, the association between PSA and PET positivity was evaluated using Mann–Whitney U test, logistic regression with log-transformed PSA, ROC analysis, and Spearman correlation with the number of positive sites.</p> Results <p>Overall, PET was positive in 91/103 patients (88.3%), negative in 8/103 (7.8%), and indeterminate in 4/103 (3.9%). Positivity was observed in all patients scanned for primary staging (42/42, 100.0%) and in 49/61 patients (80.3%) referred for recurrence. The most frequent positive sites were primary lesion (57.3%), lymph nodes (35.0%), and bone (24.3%). In recurrence, PSA was significantly higher in PET-positive than in non-positive cases (median 2.40 vs. 0.42 ng/mL, <i>p</i> &lt; 0.001). Log-transformed PSA was significantly associated with PET positivity (OR 7.40, 95% CI 2.18–25.11; <i>p</i> = 0.001), with an AUC of 0.912 (95% CI 0.828–0.974). PSA also correlated with the number of positive sites (rho = 0.620, <i>p</i> &lt; 0.001).</p> Conclusion <p>[¹⁸F]piflufolastat PET/CT on 194-cm LAFOV PET/CT showed high clinical performance in prostate cancer, with strong PSA-dependent yield in recurrence and effective depiction of site-specific disease distribution.</p>