OBJECTIVES/SPECIFIC AIMS: Clostridium Difficile Infection (CDI), a prevalent cause of diarrhea, is the most notorious hospital-acquired infection, resulting in an alarming mortality and health care utilization rates. Herein, we investigate the impact of cannabis use, which is gaining significant legalization for recreational use, on the risk of CDI. METHODS/STUDY POPULATION: We selected adult records (age ≥ 18 years) from the Nationwide Inpatient Sample 2014, and identified cannabis users and other clinical conditions using ICD-9-CM codes. With multivariate logistic modeling, we generated propensity scores for cannabis users and matched them to non-users in a 1:1 ratio (104,936:104,936). We then estimated the adjusted relative risk (aRR) for having CDI using conditional Possion regression models with generalized estimating equations [SAS 9.4]. RESULTS/ANTICIPATED RESULTS: Among the matched hospitalizations (n=209,872), cannabis usage was associated with a reduced incidence of CDI (505.8[464.7-550.6] vs. 694.9[645.8-747.70] per 100,000 hospitalizations), resulting in a 27% reduced risk of CDI (aRR:0.73[0.65-0.81]; p-value:<0.0001). Non-dependent and dependent cannabis users respectively had 22% and 78% reduced likelihood of CDI when compared to non-cannabis users (0.78[0.69-0.90] & 0.22[0.12-0.40]). Furthermore, dependent users had less risk of CDI compared to non-dependent users (0.28[0.16-0.51]). Comparatively, abusive use of other substances like alcohol and tobacco was associated with increased risk for CDI (1.30[1.13-1.49] & 1.24[1.10-1.40]) DISCUSSION/SIGNIFICANCE OF IMPACT: Unlike alcohol and tobacco abuse which are associated with elevated risk for CDI, cannabis use, is related to a decreased risk of CDI amongst hospitalized patients. Further prospective and molecular mechanistic studies are required to elucidate how cannabis impacts CDI.