The performance of vaginal drug delivery systems is dependent on their retention. This study presents a novel mathematical method to estimate the vaginal retention of semi-solids. Using creep analysis, the elastic and residual compliances are determined from the discrete retardation spectrum and used to determine the retention times (RT), defined as the time required for the formulations to enter the terminal viscous zone of deformation and hence flow. RT of commercially available products (CAP) and selected prototype formulations were determined, the estimated RT of CAP broadly aligning with their prescribed clinical usage. Candidate formulations composed of hydroxyethylcellulose (HEC, 3%/5%w/w) and polyacrylic acid (PAA, 1%/3%w/w) were manufactured using, and further diluted with simulant vaginal fluid (SVF) or simulant seminal fluid (SSF) and their RT subsequently determined. Increasing polymer concentration and pH enhanced the estimated RT whereas dilution reduced RT. Notably, the formulation composed of 5%HEC/3% PAA (SSF) maintained its RT on dilution due to swelling of suspended PAA particles, thus representing a strategy to develop vaginal semi-solids that are resistant to dilution and hence removal. The mathematical model described is reproducible, straightforward to use and is recommended as a tool in formulation development to estimate the retention of vaginal semi-solids.