Background: There is an urgent need to find new therapeutic drugs/regimens for advanced gastric cancer. Camrelizumab combined with apatinib and chemotherapy has shown a high objective response rate and survival benefit in the first- and second-line treatment of advanced gastric cancer. Therefore, we conducted a prospective, observational study to analyze the efficacy and safety of camrelizumab combined with apatinib and chemotherapy in the first- and second-line treatment of advanced gastric cancer. Methods: This was a multicenter, observational study enrolling patients aged ≥ 18 years with an ECOG PS of 0-2 and pathologically or histologically confirmed advanced gastric cancer. Results: By January 9, 2023, 207 patients with advanced gastric cancer from 32 centers were enrolled. Most patients were male (138 [66.7%]), stage IV (151 [72.9%]), and ECOG PS of 1 (145 [70.0%]) with a median age of 66 years. The degree of differentiation was mainly moderate and low (155 [74.9%]). 109 patients (52.7%) had a surgical history of the primary lesion, 123 (59.4%) had previously received chemotherapy, and 115 (55.6%) had received COVID-19 vaccine. The first-line treatment included camrelizumab plus chemotherapy for 4-6 cycles followed by apatinib in 68 patients (32.9%), and camrelizumab plus chemotherapy and apatinib in 51 (24.6%). Second-line treatment included camrelizumab plus apatinib for 35 patients (16.9%), chemotherapy and apatinib for 44 (21.3%), and other treatments for 9 (4.3%). Clinical efficacy was evaluated in 52 patients. There were 20 patients with partial response, 26 with stable disease, and 6 with progressive disease. The overall objective response rate (ORR) was 38.46% and disease control rate (DCR) was 88.46%. The ORR and DCR in the first-line setting were 50.00% and 100.00%, and ORR and DCR in the second-line setting were 16.67% and 66.67%. Furthermore, the ORR was 40.63% and the DCR was 90.63% in patients vaccinated against COVID-19 compared to 40.00% and 85% in unvaccinated patients. The median PFS and OS have not been reached. The incidence of adverse events (AEs) was 80.4% and the incidence of grade≥3 AEs was 3.5%. The most common AEs were reactive cutaneous capillary endothelial proliferation (71.3%), nausea (51.0%), leukocyte reduction (38.46%), and hypertension (13.3%). Conclusions: In this real-world study of gastric cancer, the first-line treatment showed good efficacy, suggesting early administration with combination treatment may bring more benefits to the patients. Additionally, COVID-19 vaccination did not affect the efficacy of combination treatment. Further validation of these preliminary results is warranted. Clinical trial information: ChiCTR2200059650.