OBJECTIVES/SPECIFIC AIMS: In an effort to elucidate the role of potentially cancer chemopreventive drugs, we leveraged the Mayo Clinic-Karolinska Institute collaboration to create a multidisciplinary team that included an epidemiologist, statisticians, and physicians. We performed a population-based cohort study to examine the association between low dose aspirin, non-aspirin NSAIDs, statins, metformin, other risk factors and the risk of biliary tract cancer (BTC), while assessing confounding by sex. METHODS/STUDY POPULATION: We conducted a nationwide Swedish population-based cohort study using the Swedish Prescribed Drug Registry, which virtually completely enumerates use of prescribed medications nationwide since 2005. BTC diagnosis (intrahepatic cholangiocarcinoma [iCCA], extrahepatic cholangiocarcinoma [eCCA] or gallbladder cancer [GBC]) was ascertained from the Swedish Cancer Registry. Age-scaled Cox models, with exposure as time-varying covariates, were used to calculate hazard ratios (HRs), separately for men and women. RESULTS/ANTICIPATED RESULTS: In the 5.7 million person cohort, the risk of iCCA was significantly lower in men using statins (HR 0.62,95%CI 0.39-1.00, p = 0.05), with a non-significant reduction in women. Statin use was associated with a significantly decreased risk of eCCA in both women (HR 0.60,0.38-0.94, p = 0.03) and men (HR 0.47,0.28-0.80, p = 0.01). Low dose aspirin (HR 0.76,0.60-0.97, p = 0.03) was associated with a lower risk of GBC only in women, while statins (HR 0.72,0.55-0.93, p = 0.01) showed a significantly decreased risk of GBC in women and a non-significant reduction in men. For all BTC subtypes, combined use of low dose aspirin and statins did not confer additional risk reductions beyond those achieved by statins alone. Male and female users of non-aspirin NSAIDs appeared to be at increased risk of BTC and its subtypes. Metformin did not significantly affect risk of BTC. DISCUSSION/SIGNIFICANCE OF IMPACT: Our collaborative efforts allowed us to develop the largest population-based cohort evaluating risk and protective factors for BTC. Our results provide strong evidence in favor of the chemopreventive roles of low dose aspirin and statins in a subtype- and sex-specific manner. Individual risk factors contribute to development of BTC subtypes in different magnitudes. The next steps to translate these findings into clinical practice require randomized clinical trials that validate our results and provide a more complete picture of the risk-benefit ratio.