Combined sewer overflows (CSOs) are known contributors of human fecal pollution in urban waterways. Exposure to these waterways occurs during recreational activities, including swimming, wading, and fishing. This study used quantitative microbial risk assessment (QMRA) to estimate the risk of acute gastrointestinal illness (AGI) due to recreation during CSO-impacted (< 24 h after a CSO) and non-impacted (> 24 h after a CSO) conditions. Water samples (n = 69) were collected from two creeks and one river in Philadelphia from June-August 2017-2019. HF183 concentrations were measured to estimate concentrations of five reference pathogens: Cryptosporidium, Giardia, norovirus, E. coli O157:H7, and Salmonella. Observational data on the types and frequency of recreational exposures were also collected. Results found that recreating < 24 h after a CSO increased AGI risk by 39-75%, compared to recreating > 24 h after a CSO. However, estimated health risks were still high for some exposure scenarios that occurred > 24 h after a CSO. Crudes estimates determined that recreational activities along known CSO-impacted sites may account for 1-8% of all cases of salmonellosis, cryptosporidiosis, and giardiasis in the city of Philadelphia. Findings support risk reduction strategies that aim to reduce the frequency of CSOs in urban settings and may help target risk mitigation strategies. All rights reserved, Elsevier.