Contraceptive side-effects are consistently given as the main reason why women are dissatisfied with contraception or choose not to use it. However, why some women suffer more from side-effects remains unknown. Through inductive analysis of in-depth interviews and focus groups discussions with 40 contraceptive users and 3 key informants in Central Oromia, Ethiopia, we explored women’s rationales for variation in side-effect experiences. The data first reveal the wide diversity in type and severity of side-effect experiences reported by users of contraception. Second, we found that women’s rationales for why some individuals suffer more side-effects from contraception invoke economic and physical hardship (food insecurity and heavy workloads), as well as interindividual differences in biology (one’s blood must ‘fit’ with contraception). Finally, the analysis revealed the tension many women face in trying to negotiate the trade-off between the consequences of these side-effects with those of an unwanted pregnancy. The results show the value of using a biosocial approach, which centres women’s voices and experiences, for informing the measurement of contraceptive side-effects within population health surveys and clinical trials and for gaining a greater understanding of how an individual’s social, biological, and cultural contexts drive variation in when and why different side-effects manifest.