This paper investigates the importance of women’s physiological condition, alongside sociocultural factors, for predicting the risk of discontinuation of the injectable contraceptive due to side effects in Ethiopia. Contraceptive calendar data from the 2016 Ethiopian Demographic and Health Survey were analyzed. Women aged 15–49 who had initiated the injectable contraceptive in the last two years were included in the analysis (n = 1,513). Physiological factors investigated were body mass, iron status, reproductive depletion, and physical strain. After checking for reverse causality, associations between physiological and sociocultural risk factors and discontinuation due to side effects (DSE) or discontinuation due to other reasons (DOR) were estimated using multivariate Cox proportional regression analyses. Anemia status was associated with DSE, but not DOR. Anemic women were two times more at risk of DSE compared with nonanemic women (adjusted hazard ratios [aHR] = 2.38, confidence interval [CI] = 1.41–4.00). DOR was predicted by religion, wealth, and relationship status. Accounting for diversity in physiological condition is key for understanding contraceptive discontinuation due to side effects. To reduce side effects, family planning programs might benefit from providing hormonal contraception within an integrated package addressing anemia.