Background Checkpoint inhibition has emerged as an effective treatment strategy for a variety of cancers, including in older adults. However, older patients with cancer represent a heterogenous group as they can vary widely in frailty, cognition, and physical status. Objective This study aims to investigate the association between clinical frailty and immune-related treatment toxicity, hospitalization, and treatment discontinuation due to immune-related treatment toxicity in older patients treated with checkpoint inhibitors. Methods Patients aged 70 years and older treated with checkpoint inhibitors were selected from the TENT study, IMAGINE study, and “Tolerability and safety of immunotherapy study”. Clinical frailty was assessed by the Geriatric-8 test score and World Health Organization (WHO) status. Outcomes were grades 3–5 toxicity, hospitalization, and treatment discontinuation due to toxicity during treatment. Results Of 99 patients included, 22% had comorbidities. While 33% of the patients were considered frail based on an abnormal Geriatric-8 test score of < 15, physical impairments were considered absent in 51% (WHO score of 0) and mild in 40% (WHO score of 1). Despite the limited sample size of the cohort, consistent trends were observed with patients with an abnormal Geriatric-8 test score of < 15 or a higher WHO score of 1 for having higher odds of toxicity odds ratio (OR) 2.32 (95% CI 0.41–13.02); OR 1.33 (95% CI 0.45–4.17), treatment discontinuation due to immune-related treatment toxicity OR 2.25 (95% CI 0.61–8.31); OR 2.18 (95% CI 0.7–6.73), and hospitalization due to immune-related treatment toxicity OR 3.72 (95% CI 0.39–35.4); OR 1.31 (95% CI 0.35–4.9). Moreover, in a sub-analysis, we observed that the treatment discontinuation due to immune-related treatment toxicity occurred often in patients with grade 1–2 toxicity as well. Conclusions Although not statistically significant, in older patients treated with immunotherapy in a real-life population with cancer, we observed consistent trends towards increased toxicity, hospitalization, and treatment discontinuation with increasing frailty. Larger studies are needed to confirm these exploratory results. Moreover, older patients with a lower toxicity grade 1–2 experienced early treatment discontinuation frequently, suggesting a lower tolerance of toxicity.