Background Low-grade chronic inflammation may persist in spontaneous HIV controllers (HIC), leading to non-AIDS defining events (nADEs). Methods 227 ART-naïve HIC (known HIV-1 infection ≥5 years and at least 5 last consecutive viral loads (VL) < 400 HIV RNA copies/mL) were compared with 328 patients who initiated ART ≤1 month after primary HIV-infection diagnosis, had undetectable VL within 12 months following ART initiation for at least 5 years (“ART-patients”). Incidence rates (IR) of first nADEs were compared between HIC and ART-treated-patients. Determinants of nADEs were assessed by using Cox regression models. Results All-cause nADEs incidence rates were 7.8 [5.9-9.6] per 100 person-months (pm) and 5.2 [3.9-6.4] per 100 pm among HIC and ART patients, respectively (Incidence Rate Ratio (IRR)=1.5 [95%Confidence Interval (CI95%), [1.1-2.2] and after adjustment IRR was (1.93; CI95% [1.16-3.20]). After adjustment for the cohort, demographic and immunological characteristics, the only other factor associated with all-cause nADEs occurrence was age ≥43 (vs.<43) years at the beginning of viral control (IRR=1.69 [1.11-2.56]). The most frequent events observed in the 2 cohorts were non-AIDS-related benign infections (54.6 and 32.9% of all nADEs, respectively for HIC and ART patients). No differences in cardiovascular or psychiatric events were observed. Conclusion HIC experienced two times more often nADEs than virologically suppressed patients on ART, mainly non-AIDS related benign infections. Older age was associated with nADEs occurrence, independently of immune or virologic parameters. These results do not argue in favor of expanding the ART indication for HIC but rather a case-by-case approach considering clinical outcomes such as nADEs besides immune activation.