Introduction: Acute pulmonary edema (APE) due to fluid overload is considered the most feared complication in hemodialysis patients. Various diagnostic tests have been proposed to assess the fluid status in patients with end-stage kidney failure (ESKF); among these, lung ultrasound (measuring the number of B-lines) is emerging as a promising tool to identify pulmonary congestion in this patient population. Methods: We compared the incidence of APE before and after the implementation of lung ultrasound as a routine practice in our unit. The pre (from 1 January 2007 to 31 December 2008)- and post (from 1 January 2017 to 31 December 2018)-B-line implementation periods included 98 and 108 hemodialysis patients, respectively. By accurately reviewing their electronic medical records, all episodes of APE were collected. The 10-year interval between the two periods was specifically chosen to ensure no overlap between patients of the two cohorts whereas the single-center design was adopted to minimize the influence of center effect on the study results. Results: APE episodes occurred more frequently in patients from the pre-B-line implementation group (18/98, i.e., 18.4%) compared with those from the post B-line implementation group (6/108, i.e., 5.5%) (p = 0.004). An analysis based on repeated APE events showed that the incidence rate of APE was significantly higher during the pre-implementation period (2.0 APE episodes per 100 person-months, 95% CI: 1.4–2.7) than during the post-implementation period (0.3 APE episodes per 100 person-months, 95% CI: 0.1–0.7), with an incidence rate ratio (post- versus pre-) of 0.17 (95% CI: 0.07–0.40; p < 0.001). The odds of experiencing APE episodes were 74% lower (odds ratio: 0.26, 95% CI: 0.10–0.69) in patients from the post B-line implementation period compared with those from the pre-implementation period. Notably, adjusting for potential confounders did not affect the strength of this association, which remained statistically significant (p ≤ 0.030). Finally, dominance analysis indicated that the implementation of B-lines was the primary factor explaining the difference in APE episodes between the two periods, followed by dialysis duration and intra-dialysis weight gain. Conclusions: The systematic use of lung ultrasound (a simple, easy-to-learn, rapid and non-invasive method, easily performed at the patient’s bed) in everyday clinical practice was associated with a drastic reduction in episodes of APE in hemodialysis patients. Further observational and interventional studies are needed to confirm these results.