Objective To investigate the relationship between serum phosphorus variability and mortality in maintenance hemodialysis (MHD) patients. Methods A total of 502 MHD cases from Renji hospital hemodialysis center were registered in Shanghai Registry Network from January 2007 to April 2015. They were recruited with general information, laboratory results and outcomes. According to their median of coefficient of variation (CV) of blood phosphorus, the patients were divided into high variation group (CV≥0.226 mmol/L) and low variation group (CV<0.226 mmol/L). The relationship of serum phosphorus CV with all?cause mortality and cardiovascular disease mortality was assessed respectively. Results The average age was (63.9±14.6) years, the median dialysis age was 82.0 (43.0, 139.0) months, 118 patients (23.5%) died for all cause and 64 patients (12.7%) died for cardiovascular disease. Compared with patients in low phosphorus variation group, patients had a higher all?cause mortality in high phosphorus variation group (27.7% vs 19.3%, P=0.028). Higher cardiovascular disease mortality was observed in high variation group as well, but this difference was no statistical significant (15.4% vs 10.0%, P=0.082). COX regression analysis showed that >60 years of age (HR=2.762, 95%CI 1.707?4.468, P<0.001), low hemoglobin (HR=0.466, 95%CI 0.317?0.686, P<0.001), low albumin (HR=0.555, 95%CI 0.366?0.840, P=0.005), high CV of phosphorus (HR=1.479, 95%CI 1.023 ? 2.139, P=0.037) were independent risk factors for all ? cause mortality. Moreover, >60 years of age (HR=2.666, 95%CI 1.469?4.837, P=0.001), low hemoglobin (HR=0.480, 95%CI 0.238?0.801, P=0.005), and high CV of phosphorus (HR=1.655, 95%CI 1.003?2.729, P=0.049) were independent risk factors for cardiovascular disease mortality. There was no significant statistical difference between patients phosphorus on target and patients phosphorus below target in all?cause disease mortality (P=0.065) and cardiovascular disease mortality (P=0.425). High variation group whose phosphorus on target had higher all?cause mortality and cardiovascular disease mortality than those in low variation group (29.2% vs 16.9%, P=0.047; 15.0% vs 6.0%, P=0.033). Kaplan?Meier method showed that patients with high phosphorus variation had higher all?cause (P=0.023) and cardiovascular disease mortality (P=0.047) than patients with low phosphorus variation. Conclusions The high CV of phosphorus is independently correlated with all?cause and cardiovascular disease mortality. Patients with standard ? reaching phosphorus in the low variation group have a lower mortality. A serum phosphorus level sustainably reaching the standard may improve the survival in MHD patients.