INTRODUCTION:The cancer research community increasingly question the rigidity of eligibility criteria in clinical trials. Common reasons for "screen failure" (RFSF) are well documented; however, their effect on subsequent standard therapy (SST) and outcomes is unclear. METHODS:This retrospective study evaluated patients aged ≥18 years with solid malignancy who were listed as ineligible on a screening log between February 2011 and March 2018. Patients screen-failed for biomarker results or incorrect cancer stage/prior treatment profile were excluded. Data were collected from electronic hospital records, including demographics, cancer history, RFSF, subsequent therapy, and outcomes. RESULTS:Overall, 217 patients were eligible. The most common histologies were lung (28%), melanoma, colon, and pancreatic (all 11%); 90% were metastatic. The most common RFSF were rapid disease progression (PD; 16%), performance status (PS) ≥2 (12%), and abnormal liver function tests (aLFT; 12%). After screen failure, 129/217 (59%) had SST; 9 were dose-reduced. Treatment-naïve or phase III trial-ineligible patients were more likely to receive SST than those pre-treated or phase I trial-ineligible (72/104 vs. 52/113, p = 0.0006; 71/109 vs. 15/42, p = 0.00013), respectively. RFSF stabilised/improved in 104/217 (48%); the main RFSF was co-morbidity (19/104). The most common RFSF to deteriorate were rapid PD (27/72), PS ≥2 (20/72), and aLFT with liver metastases (LM; 13/72). CONCLUSIONS:RFSF related to organ function rarely deteriorate unless directly involved with underlying malignancy. Most RFSF do not prevent patients from having SST, nor increase dose reductions, especially in treatment-naïve/phase III trial-ineligible patients. Those with RFSF of poor PS, rapid PD, and aLFT from LM are less suitable for SST. Careful broadening of trial eligibility is warranted.