Background: Pembrolizumab combined with chemotherapy has transformed the treatment of non-small cell lung cancer (NSCLC) and is now the standard of care. It has unique immune-related adverse events (irAE) that have been well defined. There is limited literature reporting its effect on the occurrence of common chemotherapy related AEs such as gastrointestinal adverse effects (GIAEs) (nausea, vomiting and diarrhea). We performed a meta-analysis to evaluate the GIAEs of pembrolizumab in non-small cell lung cancer patients treated with pembrolizumab and chemotherapy (P+C) and drew a comparison with those treated with chemotherapy alone (C). Methods: A literature search was performed in the MEDLINE database for randomized clinical trials of non-small cell lung cancer treated with pembrolizumab reporting gastrointestinal adverse effects. Articles were screened in concordance with PRISMA guidelines. Funnel plots were generated to assess publication bias. The pooled odds ratios (OR) for occurrence of GIAEs with 95% confidence intervals (CI) using random-effects models was calculated. Results: 9 studies (including data from KEYNOTE-021, 407, 189, 604, PROLUNG trial) were included in our analyses (n = 3157 patients). A clear increment in certain GIAEs (constipation (OR 1.16 (0.99- 1.37)), diarrhea (OR 1.51 (1.28- 1.78)), colitis (OR 4.39 (1.81- 10.62)), hepatitis (OR 4.67(1.79-12.18)) was noted the Pembrolizumab plus chemotherapy arm versus chemotherapy alone. No significant differences were noted in the occurrence of nausea, vomiting and pancreatitis. Conclusions: Pembrolizumab plus chemotherapy compared with chemotherapy alone has been studied extensively to highlight the survival advantages of the former therapeutic strategy. The risk of certain GIAEs (constipation, diarrhea, colitis, hepatitis) with pembrolizumab combination therapy for non-small cell lung cancer is significantly higher in comparison to chemotherapy alone. This alludes to the superadded effect of pembrolizumab on the existing AEs of chemotherapy.