Whole genome duplication, leading to polyploidy and endopolyploidy, occurs in all domains and kingdoms and is especially prevalent in vascular plants. Both polyploidy and endopolyploidy increase cell size, but it is uncertain whether both processes have similar effects on plant morphology and function, or whether polyploidy influences the magnitude of endopolyploidy. To address these gaps in knowledge, fifty-five geographically separated diploid genotypes (i.e., accessions) of Arabidopsis thaliana that span a gradient of endopolyploidy were experimentally manipulated to induce polyploidy. Both the diploids and artificially induced tetraploids were grown in a common greenhouse environment and evaluated with respect to nine reproductive and vegetative characteristics. Induced polyploidy decreased leaf endopolyploidy and stem endopolyploidy along with specific leaf area, stem height, but increased days to bolting, leaf size, leaf dry mass and leaf water content. Phenotypic responses to induced polyploidy varied significantly among genotypes but this did not affect the relationship between phenotypic traits and endopolyploidy. Our results provide the experimental support for a trade-off between induced polyploidy and endopolyploidy, which caused induced polyploids to have lower endopolyploidy than diploids. Though polyploidy did not influence the relationship between endopolyploidy and plant traits, phenotypic responses to experimental genome duplication could not be easily predicted because of strong cytotype by genotype interactions.