We aimed to identify predictors of confirmed monkeypox (mpox) among people with mpox-like illness and to develop a multivariable model for confirmed mpox.We performed an observational study using national epidemiologic surveillance data in Mexico from May to November 2022. People with mpox-like illness were reported to the Mexican Ministry of Health and real-time polymerase chain reaction was performed in clinical samples to confirm mpox. Sociodemographic and clinical data were collected with a case report form. We performed univariable logistic regressions to estimate the predictive capability of individual characteristics, reported with ORs and 95% CIs. Variables of interest were included in multivariable logistic regression models and Akaike information criterion was used to retain variables for the final model. Discrimination and calibration of the model were estimated in bootstrap resamples.A total of 5078 people were reported with mpox-like illness. Of 5078 people, 3291 (64.8%) had confirmed mpox. The strongest clinical predictors of confirmed mpox in univariable models were proctitis (OR 6.54, 5.93-7.21), inguinal adenopathy (OR 5.91, 5.36-6.52), and anogenital lesions (OR 5.45, 4.94-6.02). The final model included being a man who has sex with men (8.75, 7.37-10.38), HIV diagnosis (3.04, 2.51-3.69), inguinal adenopathy (2.24, 1.81-2.77), anogenital lesions (2.32, 1.97-2.74), and pustules (1.55, 1.32-1.81). Discrimination capability was excellent (c-statistic 0.88, 95% CI 0.87-0.89) and it was well calibrated (calibration slope 1, 95% CI 0.95-1.05).A third of people with mpox-like illness do not have mpox. Factors such as being a man who has sex with men, HIV diagnosis, inguinal adenopathy, pustules, and anogenital lesions are associated with confirmed mpox.