Introduction: Percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) requires advanced techniques and prolonged procedural efforts, often necessitating high contrast volumes, which may increase the risk of contrast-associated acute kidney injury (CA-AKI). However, evidence suggests that factors beyond contrast exposure contribute to CA-AKI, though data specific to CTO PCI remain limited. Methods: Patients undergoing contemporary CTO PCI at our university-affiliated tertiary care center were enrolled. CA-AKI was defined according to KDIGO criteria, and patients were stratified based on the presence of postprocedural CA-AKI. Baseline and procedural characteristics, including osmotic factors, were compared between the groups. The primary outcome was all-cause mortality at one year, and the secondary outcome was all-cause mortality at three years. Results: A total of 145 patients were enrolled, with a mean age of 67 years, and 75% were male. Baseline creatinine levels, electrolytes, and osmotic factors did not differ significantly between groups. Lesion parameters and J-CTO scores were also comparable. The contrast volume and procedural duration were numerically higher in patients who developed CA-AKI. Patients with CA-AKI received a higher radiation dose (22.1 vs. 13.2 Gy·cm2, p = 0.041). CA-AKI emerged as an independent predictor of all-cause mortality at one year (adjusted HR 5.3, CI [1.52–18.51], p = 0.009) but not at three years. Conclusions: In this retrospective analysis, CA-AKI was an independent predictor of all-cause mortality at one year following CTO PCI but lost predictive value at three years. Baseline renal function and contrast volume alone did not predict CA-AKI. Instead, procedural complexity, reflected by higher radiation exposure, was associated with an elevated risk of CA-AKI.