Background and Aim: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a procedure of choice for the diagnostic evaluation of submucosal and periluminal lesions. Tissue sample can be obtained by EUS-FNA cytology (FNAC) or cell block (CB). The aim of the present study is to compare diagnostic yield of EUS-FNA CB and cytology in the absence of onsite pathologist following a protocol-based EUS-FNA approach in solid lesions. Patients and Methods: Participants who underwent EUS-FNA at our center for solid submucosal or periluminal lesions (pancreas, lymph node, and liver) between 2014 and 2016 were included, retrospectively. The indication for the procedure along with the clinical and other investigation details and the final etiological diagnosis were recorded on uniform structured data forms. The diagnostic yield of cytology and CB were compared using McNemar’s test. The P < 0.05 was considered statistically significant. Results: EUS-FNA for solid lesion was performed in 130 lesions in 101 patients during the study period. Their mean age was 52.5 ± 12 years and 42.5% were female. Pancreatic masses were the most common lesions (37.7%) followed by lymph nodes (36.9%). Submucosal lesions (17.7%) and liver lesions (7.7%) accounted for rest of the cases. The overall diagnostic yield for EUS-FNAC (70%) and CB (74.6%) was not significantly different (P = 0.3) and their combined yield was 85.3%. For the 23 patients with submucosal lesion, diagnostic yield of CB (82.6%) was significantly better than cytology (47.8%, P = 0.04). Conclusions: EUS-guided CB has better yield compared to cytology in gastrointestinal submucosal lesions. The combination of CB with cytology improves the overall yield of the procedure; and hence, they should be considered complimentary rather than alternatives.