Background/Objectives: No-reflow phenomenon (NRP) is a frequent and clinically relevant complication during percutaneous coronary intervention (PCI) of saphenous vein grafts (SVGs). The Naples Prognostic Score (NPS), a composite index reflecting systemic inflammation and nutritional status, may help identify patients at increased risk before the procedure. We investigated whether NPS predicts NRP in patients undergoing PCI/percutaneous transluminal coronary angioplasty (PTCA) for SVG stenosis. Methods: In this retrospective multicenter observational study, consecutive post-coronary artery bypass grafting patients undergoing PCI/PTCA for SVG stenosis were analyzed. NRP was defined as post-procedural thrombolysis in myocardial infarction (TIMI) flow grade <3 in the absence of dissection, residual stenosis, or vasospasm. NPS (0–4) was calculated from serum albumin, total cholesterol, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. Independent predictors of NRP were assessed using logistic regression, and discrimination was evaluated by receiver operating characteristic (ROC) analysis. Results: Among 252 patients, 55 (21.8%) developed NRP. NPS was significantly higher in the NRP group than in the normal-reflow group (2.61 ± 0.95 vs. 1.73 ± 0.95; p < 0.001). In multivariable analysis, NPS independently predicted NRP (per 1-point increase: odds ratio 2.577, 95% CI 1.428–5.384; p < 0.001 for univariate and 6.077, 95% CI 3.194–11.563; p < 0.001 for multivariate analysis), together with high thrombus burden (TIMI thrombus grades 4–5). NPS showed good discrimination for NRP (AUC 0.742; p < 0.001), with 75% sensitivity and 66% specificity at the optimal cut-off. Conclusions: NPS is a simple, readily available score that independently predicts angiographic no-reflow during SVG PCI and may aid preprocedural risk stratification and tailoring of preventive strategies.