Background: Muscle invasive bladder cancer (MIBC) frequently recurs despite radical cystectomy, and new biomarkers are needed to guide treatment. DNA methylation plays a key regulatory role in cancer initiation and progression and has been correlated with prognosis in multiple cancer types. We hypothesized that methylation patterns in cfDNA can predict recurrence after curative cystectomy. Methods: Using a clinically annotated USC bladder cancer tissue archive under an IRB approved protocol, we selected 40 patients whose cancer relapsed within 3 years of radical cystectomy, as well as 46 age-matched and stage-matched patients who did not recur after 3 years of follow-up. cfDNA was extracted from the archival plasma, and samples were pooled for whole genome bisulfite sequencing (WGBS) based on pathologic stages (T2a, T2b, T3a, T3b, and T4/N+) and recurrence status. Results: Extracted cfDNA and sequencing met QC criteria, and differentially methylated regions (DMRs) were called by metlene and filtered based on > 10% methylation difference (recurrence vs. cured) and p value < 0.01. Pooled analysis across stages yielded 729 DMRs, of which 487 (67%) were hypomethylated in the recurrence groups. Unsupervised clustering of these DMRs accurately distinguished the recurrence groups. Stage-specific DMRs were also called and used to generate a list of differentially methylated genes shared across stages. Methylation by stage and pooled across stage in our recurrence groups was directly correlated with methylation in tumor tissue in publically available datasets (Basespace Correlation Engine) and was inversely correlated with TCGA expression datasets. Conclusions: WGBS was successfully performed in MIBC using cfDNA extracted from archival plasma. Methylation patterns were concordant with publically available datasets, and cfDNA hypomethylation pre-cystectomy was associated with cancer recurrence in our cohort. Additional data filtering and annotation is ongoing and will be used to define a methylation signature for validation as a biomarker predictive of recurrence in MIBC.