MOTIVATION: Mendelian randomization (MR) is a widely used approach to estimate causal effect of variation in gene expression on complex traits. Among several MR-based algorithms, transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) enables the uses of multiple SNPs as instruments and multiple gene expression traits as exposures to facilitate causal inference in observational studies. RESULTS: Here we present a Python-based implementation of TWMR and revTWMR. Our implementation offers GPU computational support for faster computations and robust computation mode resilient to highly correlated gene expressions and genetic variants. AVAILABILITY AND IMPLEMENTATION: pyTWMR is available at github.com/soreshkov/pyTWMR.