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Breast cancer–related lymphedema is a common and debilitating side effect of cancer treatment. This randomized trial compared the effect of progressive resistance- or aerobic-based exercise on breast cancer–related lymphedema extent and severity, as well as participants’ muscular strength and endurance, aerobic fitness, body composition, upper-body function, and quality of life.Women with a clinical diagnosis of stable unilateral, upper-limb lymphedema secondary to breast cancer were randomly allocated to a resistance-based (n = 21) or aerobic-based (n = 20) exercise group (12-wk intervention). Women were assessed preintervention, postintervention, and 12 wk postintervention, with generalized estimating equation models used to compare over time changes in each group’s lymphedema (two-tailed P < 0.05).Lymphedema remained stable in both groups (as measured by bioimpedance spectroscopy and circumferences), with no significant differences between groups noted in lymphedema status. There was a significant (P < 0.01) time–group effect for upper-body strength (assessed using four to six repetition maximum bench press), with the resistance-based exercise group increasing strength by 4.2 kg (95% confidence interval [CI] = 3.2–5.2) postintervention compared with 1.2 kg (95% CI = −0.1 to 2.5) in the aerobic-based exercise group. Although not supported statistically, the aerobic-based exercise group reported a clinically relevant decline in number of symptoms postintervention (−1.5, 95% CI = −2.6 to −0.3), and women in both exercise groups experienced clinically meaningful improvements in lower-body endurance, aerobic fitness, and quality of life by 12-wk follow-up.Participating in resistance- or aerobic-based exercise did not change lymphedema status but led to clinically relevant improvements in function and quality of life, with findings suggesting that neither mode is superior with respect to lymphedema effect. As such, personal preferences, survivorship concerns, and functional needs are important and relevant considerations when prescribing exercise mode to those with secondary lymphedema.