Objective To compare the impact on ¹⁸F fluorodeoxyglucose （¹⁸F-FDG） positron emission tomography （PET） image quality when block sequential regularized expectation maximization （BSREM） algorithm and ordered subset expectation maximization （OSEM） algorithm were used at various acquisition times （ATs）, and to discuss the feasibility of AT optimization with BSREM algorithm. Methods In the phantom experiment, the NEMA/IEC PET phantom was adopted. In the clinical study, 66 pulmonary nodules with high uptake values from 61 patients who underwent a ¹⁸F-FDG PET-CT examination for pulmonary nodules from March to September 2020 were included. PET images were reconstructed according to BSREM algorithm and OSEM algorithm at various ATs in both the phantom experiment and the clinical study. Coefficient of variation, signal-to-noise ratio, contrast-to-noise ratio, and activity values （uptake value in the phantom experiment; standardized uptake value in the clinical study） were compared between the above sequence images for quality evaluation. Results The phantom experiment showed that the image quality of 120 s BSREM sequence was superior to that of 120 s OSEM sequence, and the image quality of 75 s BSREM sequence was similar to that of 120 s OSEM sequence. The clinical study showed that the image quality of 120 s BSREM sequence was superior to that of 120 s OSEM sequence, and the image quality of 75 s BSREM sequence was slightly better than that of 120 s OSEM sequence. Conclusion In the PET phantom experiment and the clinical study of pulmonary nodules with high uptake values, BSREM algorithm can significantly improve the image quality as compared to OSEM algorithm, and the image quality of 75 s BSREM sequence is slightly better than that of 120 s OSEM sequence.