Background: Oral specialty drugs like abiraterone and enzalutamide are increasingly used in the management of men with advanced prostate cancer. However, the costs of these drugs can pose barriers to access and continued use, particularly in the socioeconomically disadvantaged population. The 340B program allows participating hospitals to purchase these medications at steep discounts, generating millions of dollars in savings per hospital. These savings afford them the opportunity to invest in programs (e.g., drug discounts) aimed at expanding their safety net. We assessed the effect of 340B participation on the care of men with advanced prostate cancer. Methods: A 20% sample of national Medicare claims data was used to perform a retrospective cohort study of men with advanced prostate cancer from 2012 through 2019 who received their care at a hospital. The primary outcome was the initial use of an oral specialty drug for prostate cancer and secondary outcomes included associated monthly out-of-pocket costs and adherence to treatment. To account for heterogeneity, we evaluated the effects of 1) hospital 340B participation, 2) socioeconomic status, using the social vulnerability index (SVI), and 3) the interaction between hospital 340B participation and SVI on each outcome. Results: Of the men with advanced prostate cancer, 2,237 (67%) and 1,100 (33%) received care at 340B participating and non-participating hospitals. There was no difference in the use of an oral specialty drug in men who received care at a hospital participating and not participating in the 340B program (22% vs 23% p=0.63). Conversely, when assessing variation across SVI, use of an oral specialty drug decreased with increased SVI (i.e., increased vulnerability; OR 0.95, p=0.038). However, the interaction between hospital 340B participation and SVI did not affect oral specialty drug use. Neither 340B participation, SVI, nor their interaction affected patient out-of-pocket costs. Additionally, although neither hospital 340B participation or SVI affected adherence to treatment, the interaction between 340B participation and SVI was significant (OR 1.2, p=0.040). This demonstrated that 340B was associated with better adherence to treatment among more socially vulnerable men. Conclusions: The 340B program did not affect the frequency of men with advanced prostate cancer who were started on an oral specialty drug. However, among those who were already started on therapy, 340B was associated with increased adherence to treatment in more socially vulnerable men. The underlying mechanism by which this occurred was unclear. In light of growing calls from policymakers to reform the 340B program, due to concerns regarding its effectiveness, policymakers could initially shift focus towards providing hospitals with guidance on how to effectively use savings to benefit those most in need.