In 2021, a total of 19 585 cases of medication error (ME) from 275 hospitals in 28 provincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medication. The number of hospitals reporting ME increased by 7.84% compared with that in 2020 (255 hospitals), and the number of reported ME cases increased by 23.57% compared with that in 2020 (15 849 cases). In 19 585 cases of ME reports, 278 (1.42%) were classified as grade A, 16 221 (82.82%) as grade B, 2 442 (12.47%) as grade C, 410 (2.09%) as grade D, 95 (0.49%) as grade E, 133 (0.68%) as grade F, 1 (<0.01%) as grade G, 4 (0.02%) as grade H, and 1 (<0.01%) as grade I. Among the 19 307 patients with ME of grade B to I, 10 528 (54.53%) were male and 8 779 (45.47%) were female; they aged from 1 day to 102 years, of which 2 236 (11.58%) were children (<18 years old), 9 794 (50.73%) were young and middle-aged people (≥18 to <60 years old), and 7 277 (37.69%) were elderly people (≥60 years old). A total of 234 patients were involved in serious MEs (grade E-I), including 129 (55.13%) males and 105 (44.87%) females, aged from 3 months to 99 years, of which 45 (19.23%) were children, 88 (37.61%) were young and middle-aged people, 101 (43.16%) were elderly people. Among the 16 patients with severe MEs caused by mistaken use of drugs, 14 were children, which was a double of the number in 2020 (7 in 2020); only 3 cases were reported for mistaken use of drugs in children from 2012 to 2019. The 278 grade A MEs did not involve person who triggered the ME and place where ME occurred. Among the 19 307 grade B-I MEs, 13 932 (72.16%) were triggered by physicians, 3 961 (20.52%) by pharmacists, 541 (2.80%) by nurses, 412 (2.13%) by patients and their family members, and 461 (2.39%) by other persons; the proportion of MEs triggered by physicians and patients and their family members increased year by year for 4 consecutive years (60.89%, 65.46%, and 68.05% in 2018, 2019, and 2020 by physicians, and 1.06%, 2.04%, and 2.08% in 2018, 2019, and 2020 by patients and their family members, respectively); 8 662 MEs (44.87%) occurred in clinics, 5 256 (27.22%) in hospital wards, 3 856 (19.97%) in pharmacies, 977 (5.06%) in pharmacy intravenous admixture services, 289 (1.50%) in the nurse stations, 239 (1.24%) in patients′ houses, 6 (0.03%) in the community health service stations, and 22 (0.11%) in other places; the proportion of ME occurred in clinics and at home increased year by year for 4 consecutive years (37.32%, 37.74%, and 43.24% in 2018, 2019, and 2020 in clinics, and 0.41%, 0.89%, and 1.02% in 2018, 2019, and 2020 at home, respectively). The top 3 contents of ME were wrong dosage, wrong drug class, and wrong administration frequency. The top 3 persons who discovered the ME were pharmacists, patients and their family members, and physicians. The top 3 factors causing ME were lack of related pharmacologic knowledge, tiredness, and insufficient training of medical workers.