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Background: Cisplatin is the first line of treatment in non-small cell lung cancer (NSCLC). However, its potential antineoplastic effect is hindered by its nephrotoxicity and myelotoxicity. Objective: The aim of this study is to assess the risk on myelotoxicity and nephrotoxicity from daily low-dose regimen (DLD) treatment as compared to cyclic high-dose (CHD). Methods: A retrospective cohort study was conducted by including NSCLC patients from the Amsterdam UMC and Antoni van Leeuwenhoek cancer hospital, treated with cisplatin between 2011-2012 and 2016-2018. Toxicities were defined based on common terminology criteria for myelotoxicity and nephrotoxicity (CTCAE v4.03) and categorized as overall toxicity (≥grade 1) and moderate-to-severe (≥grade 2). Adjusted relative risks (adjRR) were calculated with modified Poisson regression and hazard ratios were calculated with Cox-regression models. Results: Of the 115 NSCLC patients receiving DLD (N=62) and CHD (N=53) cisplatin treatment, 60% had ≥grade 1 anemia, 33.91% leukopenia, 31.3% neutropenia, 27.83% thrombocytopenia, 32.17 acute nephrotoxicity and 58.26% chronic nephrotoxicity. In the DLD group less ≥grade 2 toxicities were reported compared to the CHD group except for acute nephrotoxicity. However, there was a stronger association in the DLD group with ≥grade 1 leukopenia, thrombocytopenia, and nephrotoxicity. The DLD group developed significantly more ≥grade 1 leukopenia (adjRR=1.83, 95%CI 1.02-3.27), thrombocytopenia (adjRR=3.43, 95%CI 1.64-7.15) and ≥grade 2 acute nephrotoxicity (adjRR=3.02, 95%CI 1.20-7.56, p=0.019). The DLD group had a lower cumulative hazard over time for developing ≥grade 2 myelotoxicity and chronic nephrotoxicity but not for acute nephrotoxicity (adjHR=3.90, 95%CI 1.35-11.23). Conclusion: Overall, the DLD regimen was safer than the CHD regimen when assessing the risk of ≥grade 2 myelotoxicity and chronic nephrotoxicity. However, this might not be the case in patients with a higher risk of acute nephrotoxicity. After validating the results prospectively, this research could personalize cisplating treatment based on clinical characteristics of the patient not only to reach optimal effectiveness but also to minimize toxicities.