Background: Poly adenosine diphosphate ribose polymerase (PARP) enzymes aide in the repair of DNA damage. PARP inhibitors showed synthetic lethality in cancer cells and were utilized in many solid tumors with notable toxicities. Fatigue and pain are the major determinants of health-related quality of life (HRQOL) in cancer patients undergoing chemotherapy. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of HRQOL events and pulmonary toxicities. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018 were queried. Phase III RCTs that mention HRQOL events and pulmonary toxicities as adverse effects were included. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: 3188 patients from 7 phase III RCTs with breast, ovarian, and gastric cancer were eligible. Studies compared olaparib or niraparib or rucaparib versus placebo, olaparib vs single agent chemotherapy, iniparib + gemcitabine / carboplatin (GC) versus GC, veliparib + C versus C and olaparib + paclitaxel versus paclitaxel. The RR of all-grade side effects were as follows: fatigue, 1.26 (95% CI: 1.07 – 1.49, P = 0.006); decreased appetite, 1.42 (95% CI: 1.18 – 1.71, P < 0.001); arthralgia, 1.05 (95% CI: 0.83 – 1.34, P = 0.65); headache, 1.35 (95% CI: 0.99 – 1.84, P = 0.05); cough, 1.75 (95% CI: 1.17 – 2.62, P = 0.006); dyspnea, 1.40 (95% CI: 0.90 – 2.18, P = 0.12); and upper respiratory infections, 1.70 (95% CI: 0.97 – 3.00, P = 0.06). The RR of high-grade side effects were as follows: fatigue, 1.94 (95% CI: 1.24 – 3.04, P = 0.004); arthralgia, 1.37 (95% CI: 0.29 – 6.51, P = 0.68); headache, 1.09 (95% CI: 0.47 – 2.55, P = 0.83); and dyspnea, 1.02 (95% CI: 0.44 – 2.36, P = 0.95). Conclusions: The risk of developing all grades of fatigue as well as any-grade cough and decreased appetite was high in PARP inhibitors group, compared to control arm. Recognizing these toxicities and providing good supportive care is vital in enhancing patients’ quality of life.