OBJECTIVE: To examine upper limb physical function and adverse effects after axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) in patients with breast cancer to identify impairments that can inform rehabilitation strategies. DESIGN: Prospective longitudinal cohort. Upper limb measurements were studied preoperatively and 2.5 years after breast cancer treatment. SETTING: Hospital setting. PARTICIPANTS: Two groups of patients with early-stage primary breast cancer (N=391): the ALND surgery group (mean age, 55±10y) and the SLNB group (mean age, 57±10y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Arm lymphedema (≥10% increased arm volume relative to control arm volume), grip strength (in kilograms), shoulder mobility, pain intensity during isometric shoulder abduction (on a 100-mm visual analog scale), and body mass index (kg/m(2)). Parametric/nonparametric tests were used for hypothesized changes and differences, and regression analysis was used for confounding factors. RESULTS: We observed more adverse effects in women treated with ALND than with SLNB after 2.5 years (P<.05): arm lymphedema (17% vs 3%), grip strength reduction (12% vs 2%), and shoulder abduction-provoked pain (increase of 6% vs decrease of 50%). The adverse effects were similar for affected and control upper limbs for all outcomes except arm lymphedema, which occurred only on the affected side. CONCLUSIONS: Adverse effects in both affected and control/unaffected upper limb were observed after 2.5-year follow-up in both ALND and SLNB groups, but a higher prevalence was observed in the ALND group. Thus, women going through ALND surgery may benefit from further postoperative physical therapy, including resistance and strength exercise, focusing on pain management.