Background During the month of Ramadan, Muslims abstain from daytime consumption of fluids and foods, although some high-risk individuals are exempt. Because fasting's effects on the risk of acute kidney injury (AKI) have not been established, this study assesses the relationship between fasting and risk of AKI and identifies patients at high risk. Methods A single-center, retrospective, propensity-score matched, cohort study was conducted with data collected from adult patients admitted to the emergency room during Ramadan and the following month over two consecutive years (2016 and 2017). AKI was diagnosed based on the 2012 definition from the Kidney Disease: Improving Global Outcomes clinical practice guideline. Multivariable logistic regression analyses were used to examine the correlation and measure the effect of fasting on the incidence of AKI, and assess the effect of different variables on the incidence of AKI between the matching cohorts. Results A total of 1199 patients were included; after matching, each cohort had 499 patients. In the fasting cohort, the incidence of AKI and the risk of developing AKI were significantly lower (adjusted odds ratio (AOR) 0.65;95% confidence interval (CI) 0.44–0.98). The most indicative risk factors for AKI were hypertension (AOR 2.17; 95% CI 1.48–3.18), history of AKI (AOR 5.05; 95% CI 3.46–7.39), and liver cirrhosis (AOR 3.01; 95% CI 1.04–8.70). Patients with these factors or most other comorbidities in the fasting cohort had a lower risk of AKI as compared with their nonfasting counterparts. Conclusion The data show a strong reduction in the risk of developing AKI as a benefit of fasting, particularly in patients with comorbid conditions. Therefore, most patients with comorbid conditions are not harmed from fasting during Ramadan. However, larger prospective studies are needed to investigate the benefit of fasting in reducing the risk of developing AKI.