Abstract Background Monoclonal antibodies (mAb) targeting PD-1/PD-L1 have revolutionized melanoma treatment, yet data regarding effectiveness and tolerability across age groups is limited. We sought to determine the impact of age on overall survival (OS), progression-free survival (PFS), and rates of immune-mediated toxicities in patients treated with anti–PD-1/anti-PD-L1 mAb at two academic medical centers. Methods We retrospectively collected data on all patients with metastatic melanoma treated with anti-PD-1/PD-L1 mAb between May 2009 and April 2015. We used Kaplan-Meier and Cox regression analyses to assess OS and PFS and identify factors associated with these outcomes. We also compared rates of autoimmune toxicity across age groups. Results Of 254 patients, 57 (22.4%) were <50 years old, 85 (33.5%) were age 50–64, 65 (25.6%) were age 65–74, and 47 (18.5%) were ≥75 years. Across age groups, no differences existed in median OS (age <50: 22.9 months, age 50–64: 25.3 months, age 65–74: 22.0 months, age ≥75: 24.3 months) or PFS (age <50: 4.1 months, age 50–64: 6.5 months, age 65–74: 5.4 months, age ≥75: 7.9 months). The presence of liver metastases and elevated pre-treatment lactate dehydrogenase (LDH) were associated with reduced OS. Presence of liver metastasis, pretreatment LDH, BRAF mutation, and type of melanoma correlated with PFS. Overall, 110 patients (43.3%) experienced immune-mediated toxicities; 25 (9.8%) had colitis and 26 (10.2%) had endocrine toxicity. Rates of colitis, hepatitis, and pneumonitis did not differ across age groups. Conclusion We demonstrated that patients could safely tolerate anti-PD1/PDL-1 mAb therapy and achieve similar outcomes regardless of their age.