Background: There is little phase 4 data regarding the toxicity and effectiveness of contemporary metastatic castrate-resistant prostate cancer (mCRPC) treatments. We examined hospital admissions and emergency room (ER) visits and survival among patients in the Province of Ontario treated with abiraterone, enzalutamide, docetaxel, or cabazitaxel for mCRPC. Methods: We performed a population-based, retrospective cohort study of 2439 men over the age of 65 treated with abiraterone, enzalutamide, docetaxel, or cabazitaxel for mCRPC from 2003-2015 in Ontario, Canada. Outcomes were toxicity (hospitalizations and ER visits) and overall survival. We used multivariable Cox proportional hazards models with time-varying exposures to calculate hazard ratios (HR). Results: Among 2439 patients, cumulative exposure was greatest for docetaxel (n = 1886 (77.3%); 11,436 person-months), followed by abiraterone (n = 893 (36.6%); 5143 person-months), enzalutamide (n = 52 (2.1%); 351 person-months) and cabazitaxel (n = 18 (0.7%); 61 person-months). Abiraterone exposure was not significantly associated with any-cause (HR 0.88, 95% CI 0.72-1.07) or treatment-related (HR 1.09, 95% CI 0.87-1.37) hospitalizations or ER visits. Enzalutamide was not significantly associated with any-cause (HR 1.20, 95% CI 0.69-2.07) or treatment-related (HR 0.85, 95% CI 0.43-1.68) toxicity. Docetaxel exposure was associated with a significantly increased risk of any-cause (HR 1.29, 95% CI 1.15-1.44) and treatment-related (HR 1.52, 95% CI 1.33-1.74) toxicity. Cabazitaxel exposure was also associated with treatment-related (HR 5.94, 95% CI 1.87-18.92) but not any-cause (HR 2.37, 95% CI 0.59-9.63) toxicity. Patients who began CRPC treatment after the introduction of oral therapies had improved overall survival compared with those treated prior to their introduction (aHR 0.70, 95% CI 0.64-0.77). Conclusions: Among patients with metastatic CRPC, treatment with chemotherapy (docetaxel or cabazitaxel) is associated with an increased risk of hospitalizations and emergency room visits. We failed to show a significantly increased risk for patients treated with oral agents (abiraterone or enzalutamide).