AIM: To evaluate the efficacy of second-stage phacoemulsification (PE) of complicated initial cataract after vitreoretinal surgery (VRS) in patients with advanced proliferative diabetic retinopathy (PDR). METHODS: Totally 216 patients with PDR and complicated initial cataract who underwent surgery were included. These patients were divided into four groups according to their management. In the 1st group patients were subjected to a two–step surgical procedure: VRS with silicone oil tamponade was performed as the first step, followed by the second step, PE+intraocular lens (IOL) implantation+silicone oil removal. In the 2nd group PE was performed simultaneously with VRS and silicone oil tamponade. The second step differed in the removal of silicone oil from the vitreous cavity. Patients Ia (n=17) and IIa (n=17) subgroups had their tear liquid samples being examined before surgery and on the 2nd day after the 1st phase. In subgroups Ib and IIb, an angiogenesis inhibitor was implanted 10-14d before VRS at a dose of 0.5 mg once. In the 3rd group patients were subjected to a two–step surgical procedure: VRS with gas tamponade performed as the 1st step in their treatment; followed by the 2nd step, PE and the IOL implantation. In the 4th group PE performed simultaneously with VRS with gas tamponade. RESULTS: Patients in subgroup Ia and group III had better functional results than those in subgroup IIa and group IV, respectively (P<0.001). More marked inflammatory response (2-3 points) was statistically significant in patients of the IIa subgroup (P<0.001) and group IV (P<0.001) in comparison with the patients in the Ia and group III respectively. The IIa subgroup (n=9; 14.5%) showed higher incidence of neovascular glaucoma (NVG) than the Ia (n=2; 3.2%), P=0.027. There also was a higher rate of NVG in group IV (n=6; 19.3%) compared to group III (n=1; 3.1%), P=0.04. Subgroup IIa revealed a 2 to 2.5 times higher concentration of interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), and inter-cellular adhesion molecule 1 (ICAM-1) compared to subgroup Ia. CONCLUSION: PE of initial cataract at the second stage after VRS in patients with advanced PDR provides a sparing approach to surgical treatment in this category of patients and allows to improve anatomical and functional results of VRS. In addition, it contributes to reduction of number and severity of postoperative complications.