Abstract Background and Aims The incidence of patients starting haemodialysis is increasing. While Arteriovenous Fistula (AVF) stands as the preferred vascular access method, a significant proportion of AVFs experience primary failure, with rates ranging from 20% to 65%. Moreover, around 50% require reintervention due to delayed maturation, resulting in increased costs and patient morbidity. Understanding the factors involved and their influence on AVF development is paramount. This analysis aims to improve the preoperative decision-making process, advocating for a personalized patient approach, thereby increasing the likelihood of success. Method A prospective observational cohort study that included patients with chronic kidney disease either on dialysis or in the pre-dialysis stage. The study enrolled a total of 140 patients attending a multidisciplinary team appointment (including a vascular surgeon and a nephrologist) at a Tertiary Hospital Centre during the first semester of 2023, of whom 98 patients were included. Demographic characteristics, comorbidities, and vascular parameters observed through ultrasound underwent a comprehensive analysis. The newly formed fistulas were then thoroughly reassessed for maturation using both physical and ultrasound examinations. Results The cohort comprised 56.1% male, with a mean age of 71.06 ± 12.51 years. Among the newly formed fistulas, there were 35.7% (n = 35) radiocephalic fistulas, 46.9% (n = 46) brachiocephalic fistulas, and 17.3% (n = 17) brachiobasilic fistulas. Out of the total 98 AVFs, 59.2% (n = 58) AVFs were maturate and 11.22% (n = 11) AVFs had delayed maturation and were proposed for surgery or angiography procedure. Primary failure occurred in 29.6% (n = 29) AVF, with 42.9% (n = 15) occurring in the forearm, and 22.2% (n = 14) in the upper arm. The major cause of primary failure was thrombosis, accounting for 93.1% (n = 27) of cases. The analysis unveiled that the absence of immediate post-operative thrill, forearm AVFs and previous fistula failure were associated with a higher likelihood of AVF primary failure and non-maturation. Conversely, a larger vein diameter was linked with a reduced likelihood of AVF primary failure, with a Youden Index-derived cut-off of 4.25 mm, with 40.9% sensitivity and 86.2% specificity (p < 0.05). No other clinical or ultrasound factors exhibited a statistically significant impact. Conclusion This study sheds light on the challenges faced in AVF maturation due to a high incidence of primary fistula failure and a maturation rate that only slightly surpasses 50%. A larger vein diameter emerges as a significant predictor of AVF maturation. Although the cut-off point for vein diameter is frequently cited as 2 mm, this value often varies in the literature. This study underscores the importance of considering higher vein diameters, but, more importantly, it suggests that establishing a rigid and uniform cut-off for all centres may not be beneficial. It is crucial to recognize that the optimal vascular characteristics may vary based on the unique circumstances of each centre and the specific needs and features of each patient. The lack of association between demographic parameters and comorbidities with primary failure, juxtaposed with the evidence of more susceptible patients to consecutive primary failure, underscores the need for further studies to explore the unique individual circumstances that may account for this phenomenon.