Background: Alternative splicing events can represent driver aberrations in cancer the same way as mutations, copy number changes, and gene fusions. We previously identified TP63 isoforms that were associated with prognosis in patients with bladder cancer and other tumor types. However, little is known about how isoform expression heterogeneity in other genes contributes to outcomes in bladder cancer. We hypothesized that expression of alternative isoforms in bladder cancer would be associated with clinical outcomes in a manner distinct from previously seen gene level associations. Methods: To examine this, we developed a high-throughput approach to identify and characterize prognostic gene isoforms that are associated with worse prognosis using RNA-sequencing data from The Cancer Genome Atlas (TCGA) bladder cancer cohort (BLCA). To identify gene isoforms that associate with bladder cancer outcomes, we aligned patient reads using HISAT2 and quantified expression for 69,272 isoforms using the Refseq isoform definitions from NCBI and the Stringtie algorithm. We filtered our quantifications to isoforms that belong to a gene with two or more isoforms, and those that had >0.1 Log2 TPM expression. The remaining 42,798 isoforms were tested for association with overall survival using cox regression and based on the following criteria: an isoform had to have a Hazard Ratio greater than 1 with a p-value < 0.05, an FDR adjusted p-value < 0.2 for a log-rank survival statistic using 3 quantile expression thresholds (25, 50 and 75^th), and no significant gene-level association with disease prognosis. We validated our quantifications by confirming read coverage at the unique splice junctions for each isoform and by RT-PCR. We then performed differential expression and pathway enrichment analyses for tumors with or without expression of each pathogenic isoform. Results: 34 individual isoforms (from 30 genes) fit the criteria for association with survival. Several isoforms identified by our screen, such as FLNB, AXL, and COL6A3 isoforms, were previously shown to be associated with cancer outcomes in other tumor types. Expression of 7 isoforms were confirmed in human bladder cancer (2 isoforms of COL6A1, APLP2, TIAL1, and 1 isoform of FLNB) using RT-PCR. Expression of 21 of these prognostic isoforms were enriched in the aggressive basal squamous molecular subtype. Pathway analysis of TCGA BLCA tumors expressing these isoforms revealed enrichment of gene pathways associated with invasive cancer phenotypes, such as epithelial to mesenchymal transition and MYC targets. Conclusions: Specific isoforms are significantly associated with bladder cancer patient survival and suggest that splicing events in certain genes may act as driver aberrations in bladder cancer. Further work will need to be done to establish the regulatory mechanisms as well as how these isoforms contribute to cancer progression.