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Background: Some studies have indicated that the use of prokinetic agents may reduce pneumonia risk in some populations. Nasogastric tube insertion is known to increase the risk of pneumonia because it disrupts lower esophageal sphincter function. The aim of this study was to evaluate whether prokinetic agents could protect long-term nasogastric tube-dependent patients in Taiwan from being hospitalized for pneumonia. Methods: A case-crossover study design was applied in this study. Long-term nasogastric tube-dependent patients who had a first-time admission to a hospital due to pneumonia from 1996 to 2013 that was recorded in the Taiwan National Health Insurance Research Database were included. The case period was set to be 30 days before admission, and two control periods were selected for analysis. Prokinetic agent use during those three periods was then assessed for the included patients. Conditional logistic regression was used to calculate the odds ratio (OR) for pneumonia admission with the use of prokinetic agents. Results: A total of 639 first-time hospitalizations for pneumonia among patients with long-term nasogastric tube dependence were included. After adjusting the confounding factors for pneumonia, no negative association between prokinetic agent use and pneumonia hospitalization was found, and the adjusted OR was 1.342 (95% CI 0.967–1.86). In subgroup analysis, the adjusted ORs were 1.401 (0.982–1.997), 1.256 (0.87–1.814), 0.937 (0.607–1.447) and 2.222 (1.196–4.129) for elderly, stroke, diabetic and parkinsonism patients, respectively. Conclusion: Prokinetic agent use had no negative association with pneumonia admission among long-term nasogastric tube-dependent patients in Taiwan. [ABSTRACT FROM AUTHOR]